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Gastric cancer （GC） is one of the most common malignant tumors in the digestive system， with high morbidity and mortality. Early clinical symptoms of GC are not obvious， and most of them have entered the advanced stage after discovery， which greatly reduces the clinical cure rate and affects the quality of life of patients， and the prognosis is very poor. In recent years， with the continuous exploration in the field of bioinformatics， it has been found that micro-RNA （miRNA） and long non-coding RNA （lncRNA） exist as non-coding RNA （ncRNA） without translation ability， and regulate the expression levels of related signal proteins by acting on a certain target， thereby activating or inhibiting a certain signaling pathway， which plays an important role in assisting diagnosis， guiding clinical medication， and judging prognosis in the progress of GC. Chinese medicine is easily accepted by patients because of its good curative effect and less side effects. In the present basic studies， with the interaction mechanism between miRNA， lncRNA and signaling pathways as the breakthrough point， various studies on the regulation of related signaling molecules and signaling pathways by Chinese medicine have been carried out. A large number of experimental data have proved that the development of GC is closely related to the interaction of miRNA， lncRNA， and related signaling pathways， and Chinese medicine， with multi-target， multi-mechanism， and multi-pathway characteristics， affects various signaling molecules and signaling pathways and intervenes in the progress of GC cells. This paper reviewed the basic research on lncRNA， miRNA molecules， and main signaling pathways involved in the occurrence and development of GC， and summarized specific molecular mechanisms of Chinese medicine in the regulation of each signaling pathway， hoping to provide references for modern research of Chinese medicine in the intervention of GC progress at the molecular level.
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@#Objective To investigate the effects of long non-coding RNA(LncRNA) growth arrest specific transcript 5(GAS5) negatively regulating nucleophosmin 1(NPM1) on cisplatin(DDP) resistance of gastric cancer cells.Methods The normal human gastric mucosa cell line GES-1 and human gastric cancer cell lines BG3-823,MGC-803 and AGS were selected as the research objects,of which the level of LncRNA GAS5 in each cell was measured by qRT-PCR.The drug resistance of AGS cells to DDP(AGS/DDP) was induced,and the experiment was divided into control group,empty plasmid group(BC group),GAS5 nonsense interference group(pLJM-GAS5 NC group) and GAS5 overexpression group(pLJM-GAS5 group).MTT method was used to determine the effect of DDP on the proliferation of AGS and AGS/DDP cells;and the levels of NPM1,multidrug resistance 1(MDR1),excision repair cross complementation group 1(ERCC1),multidrug resistance-associated protein 1(MRP1) and N-cadherin in AGS and AGS/DDP cells were measured by Western blot.Results Compared with the normal gastric mucosa GES-1 cells,the level of LncRNA GAS5 in BG3-823 and AGS cells decreased significantly,and among them,the level of LncRNA GAS5 in AGS cells was the lowest,so AGS cells were used for the follow-up experiments.Compared with the control group,the level of LncRNA GAS5 in AGS cells of BC group and pLJM-GAS5 NC group decreased significantly,while the levels of NPM1,MDRl,ERCC1,MRP1 and N-cadherin increased significantly;compared with BC group and pLJM-GAS5 NC group,the level of LncRNA GAS5 in AGS/DDP cells of pLJM-GAS5 group increased significantly,while the levels of NPM1,MDR1,ERCC1,MRP1 and N-cadherin decreased significantly;after treatment with DDP of the same concentration(except 0 μmol/L),compared with the control group,the inhibition rate of AGS/DDP cell proliferation in BC group and pLJM-GAS5 NC group decreased significantly;compared with BC group and pLJM-GAS5 NC group,the inhibition rate of AGS/DDP cell proliferation in pLJM-GAS5group was significantly higher.The semi inhibitory concentration(IC_(50)) of DDP on AGS/DDP cells in pLJM-GAS5 group for 48 h was(65.38±5.04) μmol/L,which was significantly lower than(120.74±4.17) μmol/L and(120.24±4.29) μmol/L in BC group and pLJM-GAS5 NC group.Conclusion Up-regulating the level of LncRNA GAS5 in AGS/DDP cells can reverse the drug resistance of AGS/DDP cells,which may be related to the down-regulation of NPM1expression
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@#ObjectiveTo establish models of Dengue virus type Ⅲ（DENV-3,DV-3）infection and antibody dependent enhancement(ADE)infection at the acute monocytic leukemia cells(THP-1),investigate the differential expression of long non-coding RNAs(LncRNAs),map the competitive endogenous RNA(CeRNA)regulatory network and predict the translation function of LncRNAs.MethodsThe culture supernatant was harvested 6 d after C6/36 cells were infected with DENV-3,the virus titer was determined by CCID50,and the type and full-length genome amplification were identified by PCR;The DENV-3 standard plasmid was amplified,identified by PCR,and the standard curve was drawn;THP-1 cells were divided into negative control group(THP-1),direct infection group(DV-3),ADE group and blank control group[1640(-)]. After 48 h of infection,the total RNA was extracted and the copy number of intracellular virus nucleic acid was measured;Through the whole transcriptome sequencing technology,the CeRNA regulatory network was constructed for the top five up-regulated and down-regulated LncRNAs in THP-1 vs DENV3,THP-1 vs ADE,DENV3 vs ADE groups,and the functions of their coding proteins were analyzed.ResultsC6/36 cells infected with DENV-3 for 3 d showed obvious cell fusion,vacuoles and abscission;The virus had a titer of about 1. 0 × 104. 64PFU/mL and was identified as DENV-3 by PCR specific primers,of which the complete gene sequence was obtained;The number of viral nucleic acid copies in ADE group was significantly higher than those in DV-3 group and blank control group;In THP-1 vs DENV-3,the expression of cytohesin interacting protein(CYTIP)was predicted to be up-regulated;In THP-1 vs ADE,the expression of kinesin family5A(KIF5A)was predicted to be down-regulated;In DENV-3 vs ADE,the expression of cluster differentiation antigen 9(CD9)and insulin like growth factor 2(IGF2)was predicted to be up-regulated. All of these differential LncRNAs had open reading frames(ORFs). Except Lnc-SH3BP1 and Lnc-RPL41,all of the other LncRNAs had internal ribosome binding site(IRES).ConclusionIn DENV-3 infection of THP-1 cells and ADE infection mediated by DENV-3,the expression of LncRNAs has changed significantly,and may regulate the process of infection through a variety of biological functions,which is helpful for a deeper understanding of the mechanism of ADE infection.
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Breast cancer is a malignant tumor that seriously endangers women's lives. The prognosis of breast cancer patients differs among molecular types. Compared with other subtypes, triple-negative breast cancer (TNBC) has been a research hotspot in recent years because of its high degree of malignancy, strong invasiveness, rapid progression, easy of recurrence, distant metastasis, poor prognosis, and high mortality. Many studies have found that long non-coding RNA (lncRNA) plays an important role in the occurrence, proliferation, migration, recurrence, chemotherapy resistance, and other characteristics of TNBC. Some lncRNAs are expected to become biomarkers in the diagnosis and prognosis of TNBC, and even new targets for its treatment. Based on a PubMed literature search, this review summarizes the progress in research on lncRNAs in TNBC and discusses their roles in TNBC diagnosis, prognosis, and chemotherapy with the hope of providing help for future research.
Subject(s)
Humans , Female , Triple Negative Breast Neoplasms/genetics , RNA, Long Noncoding/genetics , Biomarkers, Tumor/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.
Subject(s)
Humans , RNA, Untranslated/genetics , RNA , Myocardial Infarction/genetics , Biomarkers , Computational Biology , MicroRNAs/geneticsABSTRACT
Long non-coding RNA (lncRNA) are non-coding RNA (ncRNA) greater than 200nt inlength, which were initially considered as transcriptional " junk" with no biological function. As researchprogressed, lncRNA were found to be involved in many biological regulatory processes, such aschromosome silencing, chromatin modification, transcriptional activation and interference. Thesebiological regulatory processes are closely related to the structure and spatial and temporal specificexpression of lncRNA. In addition, the corresponding regulatory mechanisms of lncRNA with differentstructures and locations are different. When lncRNA are located in the nucleus, they mostly regulate geneexpression at the transcriptional level and epigenetically, including histone modifications, DNAmethylation, chromosome remodeling and other modification processes. In contrast, lncRNA in thecytoplasm mostly play regulatory roles at the post-transcriptional and translational levels, and themechanisms of action and functions of lncRNA vary among different organelles, all of which illustrate theimportance of the location of lncRNA on their functional performance. In addition, exosomes are also richin lncRNA, and these lncRNA can be delivered to the corresponding sensitive cells through intercellularcommunication to generate the corresponding regulatory mechanisms. In addition, aberrant expression oflncRNA in different structures is often a key factor in the development and progression of related diseasesand cancers. Studying the enrichment of lncRNA in different subcellular structures can help understandthe specific roles played by lncRNA in regulating body homeostasis, disease and cancer occurrence anddevelopment, as well as growth and development of plants and animals, as well as provide a newtheoretical basis for subsequent studies on targeted therapies and improving animal productionperformance. This paper outlines the latest research progress on the different regulatory mechanisms oflncRNA in chromosomes, membraneless substructures, cytoplasm (endoplasmic reticulum, ribosomes, mitochondria, lysosomes), exosomes and other locations, as well as describes the processes of relateddiseases and cancers caused by lncRNA abnormalities within the corresponding structures. Finally, anoutlook on lncRNA research is given with the aim of providing a corresponding theoretical basis for futurestudies.
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Diabetes is a clinical syndrome caused by a variety of factors. It often causes multiple systemdamage, leading to chronic progressive lesions of the eye, kidney, blood vessels, heart, nerves and otherorgans. At present, its etiology and pathogenesis are not fully clarified, and there is a lack of effectivecure. Further exploration of the molecular regulatory mechanisms that drive diabetes and itscomplications, identifying specific biomarkers and molecular therapeutic targets, is undoubtedly aneffective strategy to prevent the onset and development of diabetes and improve the quality of life ofpatients. Long non-coding RNA (lncRNA) is an important regulator of body normal activity and diseasedevelopment. Abnormal expression and mutation are one of the main causes of diabetes and many otherdiseases. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a newly discovered lncRNA molecule inrecent years. It has attracted much attention because of its important regulatory role and diverse biologicaleffects in diabetes and its complications. This article summarizes the molecular regulation mechanism andrelated biological functions of lncRNA NEAT1 in diabetes and its complications in order to provide a newscientific reference for early prevention, diagnosis and molecular targeted therapy of diabetes.
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Long non-coding RNA KCNQ1OT1 is highly expressed in a variety of tumors, but there are few studies in gastric cancer and the results are inconsistent. The relevant research of its specific mechanism in gastric cancer is also scarce. Through the analysis of several TCGA public databases, we found that KCNQ1OT1 was generally highly expressed in gastric cancer, and the prognosis of gastric cancer patients with a high expression of KCNQ1OT1 was poor. The expression of KCNQ1OT1 is closely related to many clinical factors of gastric cancer, especially the mutation of TP53, and its expression is significantly related to immune cell infiltration. KCNQ1OT1 is generally highly expressed in gastric cancer cell lines. Knockdown of KCNQ1OT1 can inhibit the proliferation of gastric cancer cell lines. Co- expression network analysis showed that its expression was closely related to tumor metabolism. Glutaminase 1 (GLS1) is generally highly expressed in gastric cancer, which is closely related to a poor prognosis. There is a significant correlation between the expression of KCNQ1OT1 and GLS1. Knockdown of KCNQ1OT1 can inhibit the expression of GLS1 mRNA, and overexpression of GLS1 can partially rescue the proliferation of gastric cancer cells caused by knockdown of KCNQ1OT1. Therefore, we speculate that KCNQ1OT1 may regulate the growth of gastric cancer cells through GLS1. Our study explored the role of KCNQ1OT1 in gastric cancer through bioinformatics database and experiments, suggesting that KCNQ1OT1 may promote the development of gastric cancer by regulating glutamine metabolism, which provides a new target for the clinical research on targeted treatment in gastric cancer.
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AIM: To investigate the expression and diagnostic value of long non-coding RNA(LncRNA)hypoxia-inducible factor 1 alpha antisense RNA 1(HIF1A-AS1)in serum of patients with proliferative diabetic retinopathy(PDR).METHODS: A total of 160 patients with diabetic retinopathy(DR)admitted to our hospital from July 2019 to July 2021 were selected as the research objects. According to the degree of disease, they were divided into PDR group(80 cases)and nonproliferative diabetic retinopathy(NPDR)group(80 cases). At the same time, 100 healthy cases in our hospital were selected as the control group. Detect and compare serum triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), fasting blood glucose(FBG)and the level of glycosylated hemoglobin A1c(HbA1c); The expression level of LncRNA HIF1A-AS1 in serum was detected by real-time fluorescence quantitative PCR(qRT-PCR)method; Logistic regression was used to analyze the risk factors that affected the occurrence of PDR; Receiver operating characteristic curve(ROC)was used to analyze the clinical value of LncRNA HIF1A-AS1 level in the diagnosis of PDR. RESULTS: The expression level of LncRNA HIF1A-AS1 in the serum of the patients in the PDR group was significantly higher than that in the NPDR group and the control group, and the NPDR group was higher than the control group(P<0.05); The course of disease, HbA1c, TC, TG, LDL-C, FBG levels in the PDR group and the NPDR group were significantly higher than those of the control group, the HDL-C level in the PDR group was significantly lower than that in the control group(P<0.05); The level of LncRNA HIF1A-AS1 was positively correlated with the course of disease, HbA1c, TC, TG, LDL-C and FBG(P<0.05), and negatively correlated with HDL-C(P<0.05); Logistic regression analysis showed that the LncRNA HIF1A-AS1, course of disease, FBG, HbA1c, TC, TG, LDL-C were all risk factors for PDR(P<0.05); ROC results showed that the area under the curve(AUC)of the LncRNA HIF1A-AS1 level predicting PDR was 0.766(95%CI: 0.692～0.829), the corresponding sensitivity was 66.25% and the specificity was 78.75%.CONCLUSION: The level of LncRNA HIF1A-AS1 in the serum of PDR patients is up-regulated, it is a risk factor for the occurrence of PDR and it can be used as a potential serological indicator for predicting the occurrence of PDR.
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Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely
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ILF3 antisense RNA 1 (ILF3-AS1), the antisense RNA of interleukin enhancer binding factor 3 (ILF3), is a lncRNA located on chromosome 19p13. 2. ILF3-AS1 played a key role in the occurrence and development of a variety of tumors, but its role in cervical cancer had not been explored yet. Therefore, we first used TCGA and GTEx database to conduct bioinformatics analysis. The results suggested that ILF3-AS1 was down-regulated in cervical cancer tissues (P < 0. 001) and was associated with a good prognosis (P = 0. 045). The qRT-PCR experiment showed that expression of ILF3-AS1 in cervical cancer tissues and SiHa, HeLa, CaSki cervical cancer cell lines was lower than that in control groups. Subsequently, overexpressing of ILF3-AS1 can significantly inhibit the cancer cell viability and stimulate apoptosis (P<0. 001). Analysis using the Star Base v3. 0 database suggested that ILF3-AS1 can target miR-130a-3p; while miR-130a-3p may target PTEN. The qRT-PCR test showed that the expression of miR-130a-3p in cervical cancer was significantly higher than that in normal cervical tissues (P < 0. 01). The results of the luciferase reporter assay showed that ILF3-AS1 can specifically bind to miR-130a-3p (P<0. 01). After overexpression of ILF3-AS1 in HeLa cells, the expression of miR-130a-3p was significantly down-regulated (P < 0. 01). Co-transfection with pcDNA3. 1-ILF3-AS1 and miR-130a-3p mimics, the inhibitory effect of LF3-AS1 on cell proliferation can partially be reversed (P<0. 001). After HeLa cells overexpressed ILF3-AS1, the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) mRNA (P < 0. 001) and proteins (P < 0. 001) significantly increased; when miR-130a-3p mimics was simultaneously used in HeLa cell, the increased expression of PTEN mRNA (P <0. 001) and proteins (P < 0. 001) was notably inhibited. In summary, ILF3-AS1 inhibited the proliferation of cervical cancer cells by sponging miR-130a-3p to regulate the expression of PTEN.
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Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) that are more than 200 nucleotides in length, without protein-coding functions. More than 90% of the transcripts from the genome are ncRNA transcripts. LncRNAs have been determined to play unique roles in various biological processes with their specific structures and functions, and have emerged as a hot spot in gene-characteristics, function-identification, and biological process regulation. Previous work has confirmed that lncRNAs are involved in pathogenesis of clinical diseases, especially in tumorigenesis. In the postgenomics era, prevention, diagnosis and prognosis in certain diseases could be processed by detection on lncRNA expression alteration, phenotype changes and molecular mechanisms that are involved. Here, we defined lncRNAs, listed the strategies and methods of genetic identification, enumerated methods in spatial structure inspection and functional identification, and showed the classification of lncRNAs. Moreover, lncRNA participated in tumorigenesis. We took the most classic tumor suppressor p53 as an example, as p53-related lncRNAs are involved in colorectal cancer (CRC). We summarize the expression alterations, interaction molecules and signaling pathways of these lncRNAs Finally, the clinical application value of these lncRNAs are estimated. Collectively, lncRNAs may function as biomarkers, and will provide series of brand new, accurate and unique targets for diverse diseases including CRC.
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The skeletal muscle is an important part of the animal body, which is closely related to body movement, energy consumption, production performance and its development process is regulated by many factors. The molecular mechanism of skeletal muscle growth and development is not only closely related to animal husbandry production, but also provides a theoretical basis for the treatment of muscle dis-eases, such as amyotrophic muscular dystrophy, and so on. Non-coding RNA (ncRNA) is a kind of RNA without coding ability, in which circular RNA (circRNA), long non-coding RNA (lncRNA) and micro RNA (miRNA) have been proved to play an important role in the development of skeletal muscles. miR-NA can specifically bind to the 3′ untranslated region (3′ UTR) of the target gene through its seed se-quence, so as to inhibit the translation process of the target gene or directly degrade the target gene, and become a prominent participant in a variety of biological processes. Studies have shown that circRNA, ln-cRNA, pseudogenes and mRNA with miRNA response elements (MRE) can competitively combine miRNA to regulate gene expression, forming a competing endogenous RNA (ceRNA) regulatory network model. This hypothesis subverts the previous concept of unidirectional regulation of target genes by miRNA, and endows them with new biological functions in transcriptome, which is of great biological significance. In recent years, it has been found that ceRNA plays an important regulatory role in the growth and development of skeletal muscles. This paper reviews the role of miRNA, lncRNA and circRNA in the proliferation and differentiation of animal skeletal muscle cells, which is an important member of ceRNA mechanism, in order to broaden the research direction of skeletal muscle mechanism and provide new ideas for the development of animal husbandry and the treatment of muscle diseases.
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@#[Abstract] Objective：To study the expression of long non-coding RNA(lncRNA) titin antisense RNA1 (TTN-AS1) in lung adenocarcinoma (LUAD) tissues, and explore its relationship with clinicopathologic characteristics and prognosis of LUAD patients. Methods: The TTN-AS1 expression in LUAD data set was analyzed using TCGAdatabase. 52 pairs of tumor tissues and matched para-carcinoma tissues from LUAD patients, who underwent surgical resection and were later pathologically conformed in Fourth Hospital of Hebei Medical University between Jan. 2014 and Jan. 2015, were used in this study. qPCR was performed to detect TTN-AS1 expression in the specimens. Then, the correlations between TTN-AS1 expression and clinicopathologic characteristics were analyzed. Survival analysis was used to determine the significance of TTN-AS1 expression for predicting the prognosis of LUAD patients. Results: TCGAdatabase analysis and qPCR results showed that TTN-AS1 expression in LUAD tissues was significantly higher than that in normal lung and para-carcinoma tissues (both P<0.01). TTN-AS1 expression in LUAD tissues was significantly correlated with the TNM stage and lymph node metastasis (P<0.05), but not correlated with gender, age, tumor invasion range (P>0.05). Kaplan-Meier univariate analysis result demonstrated that the patients with high TTN-AS1 expression had shorter post-operative disease-free survival (DFS) and overall survival (OS) than those patients with low TTN-AS1 expression (all P<0.01). Cox proportional hazard regression model result demonstrated that wider tumor invasion range, positive lymph node metastasis and high TTN-AS1 expression were significantly correlated with shorter postoperative DFS and OS (P<0.05). Conclusion: TTN-AS1 was highly expressed in LUAD tissues, and closely correlated with TNM stage and lymph node metastasis of LUAD patients (all P<0.05). High expression of TTN-AS1 is significantly correlated with shorter DFS and OS, indicating that TTN-AS1 may be a biomarker for predicting poor prognosis of LUAD patients.
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@#[Abstract] Objective: To investigate the effect of long non-coding RNA (lncRNA)-CCAT2 on the proliferation and cell cycle of cervical cancer cells. Methods: The expression of CCAT2 in 3 cervical cancer cell lines (HeLa, C-33A, and CaSki) was detected by qPCR and the cell line with the highest expression level was selected for subsequent experiments. CCAT2 overexpression and interference vectors were designed and synthesized. After transfection, qPCR was performed to detect the transfection efficiency. The cells were divided into 5 groups: control, sh-EV (empty vector), overExp-EV , sh-CCAT2, and overExp-CCAT2. MTT assay was performed to evaluate cell viability. Flow cytometry was performed to measure cell cycle. WB was performed to detect the expressions of Ki67, cyclin D1, and cyclin dependent kinase 4 (CDK4). Results: Among HeLa, C-33A, and CaSki cells, the highest expression of CCAT2 was found in CaSki cells. CCAT2 overexpression and interference vectors were successfully transfected into the CaSki cells. Compared with the control group, the cells viability and proliferation in the sh-CCAT2 group was significantly decreased (all P<0.01), the proportion of cells in the G1 phase was significantly increased (P<0.01), and the expression levels of Ki67, cyclin D1, and CDK4 were significantly decreased (all P<0.01). However, in the overExp-CCAT2 group, the cell proliferation was enhanced and the expression levels of Ki67, cyclin D1, and CDK4 were significantly increased (all P<0.01). Conclusion: CCAT2 affects proliferation and cell cycle of cervical cancer cells by regulating the expressions of their associated proteins.
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@#[Abstract] Objective: To investigate the expression of long non-coding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) in esophageal squamous cell carcinoma (ESCC) tissues, and to analyze its relationship with clinicopathological features and prognosis of ESCC patients. Methods: The expression of DGCR5 in ESCC data set from TCGA database was analyzed by bioinformatics method. Sixty pairs of ESCC tissues and para-cancerous tissues resected at the Fourth Hospital of Hebei Medical University from August 2016 to March 2017 were collected for this study. The expression of DGCR5 in ESCC tissues was detected by qPCR. The correlation between the expression of DGCR5 and the clinicopathological features and prognosis of ESCC patients was analyzed. Results: TCGAdatabase analysis showed that the expression of DGCR5 in ESCC tissues was significantly higher than that in normal esophageal tissues (P<0.01). The expression of DGCR5 in ESCC tissues was significantly higher than that in para-cancerous tissues (P<0.01). The expression level of DGCR5 was significantly correlated with TNM staging and lymph node metastasis in ESCC patients (all P<0.05). Kaplan-Meier univariate analysis showed that the 2-year survival rate of ESCC patients with high DGCR5 expression was significantly lower than that of patients with low expression (P<0.05). Conclusion: DGCR5 is highly expressed in ESCC tissues and is closely related to TNM staging, lymph node metastasis and poor prognosis, which may serve as a molecular marker for early diagnosis and prognosis prediction of ESCC.
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@# Objective: To investigate the effect of long non-coding RNA (lncRNA) lung cancer associated transcript 1 (LUCAT1) on proliferation and migration of clear cell renal cell carcinoma (ccRCC) 786-O cells and the underlying mechanism. Methods: A total of 40 pairs of pathologically confirmed tumor tissues and corresponding adjacent normal tissues from ccRCC patients, who underwent surgical resection in the Department of Urology, the First People's Hospital of Yichang during June 2013 and June 2017, were selected for this study. ccRCC cell lines (786-O, ACHN, UM-RC-2) and normal renal epithelial KiMA cells were also used in this study. qPCR was used to detect the mRNA expressions of LUCAT1, miR-199a-5p and hypoxia inducible fator 1α (HIF-1α) in above mentioned tissues and cell lines; CCK-8 assay was used to evaluate the proliferation of 786-O cells; Transwell assay was used to evaluate the migration of 786-O cells; Dual luciferase reporter gene assay was performed to validate the relationship between LUCAT1 and miR-199a-5p; and Western blotting was conducted to detect the effect of LUCAT1 and miR-199a-5p on the protein expression of HIF-1α. Results: LUCAT1 was significantly up-regulated in ccRCC tissues and cell lines (all P<0.01), and its knockdown significantly inhibited the proliferation and migration of 786-O cells (all P<0.01). miR-199a-5p was low-expressed in ccRCC tissues and cell lines (all P<0.01), StarBase analysis showed that LUCAT1 contained a conserved target site for miR-199a-5p. miR-199a-5p exerted significant suppression on the luciferase activity of LUCAT1-Wt (P<0.01), and LUCAT1 knockdown significantly reduced miR-199a-5p expression (P< 0.01). LUCAT1 was low-expressed in 786-O cells transfected with miR-199a-5p mimics, however, it was attenuated after co-transfection with LUCAT1. The mRNA and protein expressions of HIF-1α in 786-O cells transfected with miR-199a-5p mimics were up-regulated, which was then reversed by LUCAT1 over-expression (P<0.05 or P<0.01). miR-199a-5p over-expression suppressed the proliferation and migration of 786-O cells, which was partially attenuated by LUCAT1 transfection (P<0.05 or P<0.01). Conclusion: LUCAT1 exerts oncogenic function in ccRCC via regulating miR-199a-5p/HIF-1α axis.·
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@#[Abstract] Objective: To explore the regulatory effect of long non-coding RNA (lncRNA) SNHG5 on invasion and migration of hypoxia-induced hepatocellular carcinoma (HCC) cells. Methods: A total of 20 pairs of cancer and para-cancerous tissue specimens resected from HCC patients in the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to June 2018, and human HCC cell lines (HepG2, MHCC-97L, MHCC-97H , Huh7) as well as immortalized human liver LO2 cells were collected for this study. Bioinformatics methods were used to analyze the binding sites between hypoxia-inducible factor 1α (HIF-1α) and SNHG5. pCMVHIF-1α and shRNA-SNHG5 (sh-SNHG5) plasmids were transfected into HCC cells, respectively. qPCR was used to detect the expres‐ sion level of SNHG5 in HCC tissues and hypoxia-induced HCC cells. Western botting was used to detect the expression level of HIF-1α protein in HCC cells, and Transwell chamber method was used to detect the migration and invasion ability of HCC cells after SNHG5 si‐ lence under normoxia and hypoxia condition. Results: Compared with para-cancerous tissues and immortalized human liver LO2 cells, the expression of SNHG5 was significantly up-regulated in HCC tissues and cell lines (all P<0.01). Hypoxia promoted the expression level of SNHG5 in HCC cells, and its mechanism might be related to the combination of hypoxia-activated HIF-1α and SNHG5 promoter to promote its transcription. Hypoxia promoted the invasion and migration ability of HepG2 and MHCC-97L cells (all P< 0.01), but knockdown of SNHG5 significantly inhibited the invasion and migration ability of HepG2 and MHCC-97L cells under hy‐ poxic conditions (all P<0.01). Conclusion: SNHG5 is highly expressed in HCC tissues and cell lines and plays an important role in the invasion and migration of HCC cells induced by hypoxia.
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@#Objective: To investigate the expressions of miR-144 and lncRNA DNAJC3-AS1 in breast cancer tissues and their effects on chemo-resistance of breast cancer MCF-7 cells. Methods: A total of 196 pairs of breast cancer tissues and corresponding adjacent normal tissues collected between January, 2012 and December, 2016 in Department of Oncology, 3201 Hospital were used for this study. The relative expressions of DNAJC3-AS1, DNAJC3 and miR-144 in collected tissues were determined using qPCR, and their impact on the survival of BC patients was also analyzed. The targeted binding relationship between DNAJC3-AS1 and miR-144 was verified by Luciferase reporter gene assay. DNAJC3-AS1 over-expression plasmid and miR-144 mimics were transfected into MCF-7 cell lines respectively, and qPCR was used to verify the transfection efficiency. The effects of DNAJC3-AS1 and miR-144 overexpression on proliferation and cisplatin sensitivity of MCF-7 cells were verified by CCK-8 assay. Results: DNAJC3-AS1 and its host gene DNAJC3 were highly expressed in BC tissues (all P<0.01), and these two were positively correlated (r=0.451, P<0.01); in addition, patients with high expressions of DNAJC3-AS1 and DNAJC3 had a shorter survival period (all P<0.01). miR-144 was highly expressed in BC tissues (P<0.01) and negatively correlated with DNAJC3-AS1 (r=-0.524, P<0.01). The average over-expressionfold for DNAJC3-AS1 was 13.47 (P<0.01), while the fold for miR-144 was 20.27 (P<0.01). Bioinformatics analysis and fluorescence reporter gene assay confirmed that DNAJC3-AS1 could specifically bind to miR-144. MCF-7 cell lines over-expressing DNAJC3-AS1 and miR-14 were successfully constructed; compared with control group, cells in DNAJC3-AS1 over-expression group exhibited significantly enhanced proliferation and reduced cisplatin-sensitivity (all P<0.01), while the cells in miR-144 over-expression group showed significantly enhanced drug sensitivity (P<0.01). Conclusion: miR-144 and lncDNAJC3-AS1 were highly expressed in BC tissues, miR-144 promotes cisplatin sensitivity of BC MCF-7 cells through targeting DNAJC3-AS1.
ABSTRACT
Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies, which makes its pathogenesis an important target for research. A growing number of studies have shown that non-coding RNA (ncRNA), including microRNA (miRNA) and long non-coding RNA (lncRNA), plays a significant role in tumorigenesis. This review summarizes the roles of miRNA and lncRNA in the progression, diagnosis, and neoadjuvant chemotherapy of TNBC. Aberrantly expressed miRNA and lncRNA are listed according to their roles. Further, it describes the multiple mechanisms that lncRNA shows for regulating gene expression in the nucleus and cytoplasm, and more importantly, describes lncRNA-regulated TNBC progression through complete combining with miRNA at the post-transcriptional level. Focusing on miRNA and lncRNA associated with TNBC can provide new insights for early diagnosis and treatment-they can be targeted in the future as a novel anticancer target of TNBC.