LncRNA CYTOR knockdown inhibits tumor development via regulating miR-503-5p/PCSK9 in lung adenocarcinoma.

BACKGROUND: The intricate biological mechanism underlying lung adenocarcinoma (LUAD), characterized by a deficiency of distinctive biomarkers, remain elusive. The presence of Long non-coding RNAs (lncRNAs) have been established to play a role in carcinogenesis. Nevertheless, the regulatory effects and mechanisms of lncRNA CYTOR in LUAD have yet to be elucidated. METHODS: In this study, RT-qPCR and Western blot were adopted to examine gene mRNA and protein expression, respectively. Cell proliferation was evaluated by CCK-8 assays. Transwell was performed to assay cell migration and invasion. The function of CYTOR in vivo was investigated through a xenograft animal model. RESULTS: We observed an apparent upregulation of CYTOR in LUAD. Silencing CYTOR significantly reduced proliferation, migration, and invasion capabilities of LUAD cells. Mechanism analysis indicated that CYTOR targeted the miR-503-5p/PCSK9 axis. Additionally, inhibiting of miR-503-5p partially reversed the inhibitory effects of CYTOR silencing on the malignant progression of LUAD cells. Animal experiments revealed that CYTOR/miR-503-5p/PCSK9 curbed tumor formation of nude mice in vivo. CONCLUSION: These findings demonstrated that lncRNA CYTOR acted as an oncogene in LUAD, regulating tumor malignant progression through the miR-503-5p/PCSK9 axis. This study unveiled a new regulation mechanism of LUAD progression, offering potential therapeutic targets for LUAD.

Integration of single-cell and bulk RNA sequencing data reveals that CYTOR is a potential prognostic and immunotherapeutic response marker for skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is a highly malignant tumor that is prone to immune escape and distant metastasis. Immunotherapy is considered to be the best treatment for patients with SKCM. However, not all patients benefit from it. We observed a significant differential expression of the lncRNA CYTOR in patients with SKCM based on single-cell and bulk RNA sequencing data mining results. The results showed that compared to normal tissue lncRNA CYTOR expression was significantly upregulated in SKCM tissue. Subsequently, we validated this finding in clinical samples, and we also found that the expression of lncRNA CYTOR in SKCM was higher as it progressed. lncRNA CYTOR was differentially expressed in patients who responded to immunotherapy, suggesting that it may serve as a biomarker to predict the efficacy of SKCM immunotherapy. In-depth analysis revealed that lncRNA CYTOR expression was strongly correlated with immune cell infiltration, immune response, and immune checkpoint expression. Meanwhile, our experiments revealed that CYTOR affects SKCM cell invasion and clone formation and is associated with the activation of the EMT pathway. In summary, our findings illustrate, for the first time, the value of CYTOR as a potential prognostic and immunotherapeutic response marker in SKCM.

Chlamydia trachomatis upregulates lncRNA CYTOR to mediate autophagy through miR-206/MAPK1 axis.

Chlamydia trachomatis infection can be regulated by autophagy-related genes. LncRNA CYTOR has been proven to be involved in autophagy. In this research, we investigated the role of CYTOR in autophagy induced by C. trachomatis and the potential mechanisms. After C. trachomatis infection, CYTOR and MAPK1 were up-regulated and miR-206 was down-regulated, meanwhile, the autophagy-related protein Beclin1 and LC3-Ⅱ/LC3-Ⅰ ratio were increased. Interference with CYTOR or overexpression with miR-206 downregulated the autophagy-related protein Beclin1 and the number of autophagic spots LC3, decreased the protein ratio of LC3-II/LC3-I, and upregulated the expression of P62 protein. The luciferase reporter assay confirmed that CYTOR acted as a sponge for miR-206 to target MAPK1. In addition, CYTOR promoted autophagy induced by C. trachomatis infection through the MAPK1/ERK signaling pathway activation. Taken together, we have identified a novel molecular mechanism that the CYTOR/miR-206/MAPK1 axis was involved in the regulation of autophagy in C. trachomatis infection. This work provides an experimental basis for elucidating the pathogenesis of C. trachomatis for the treatment, prevention and control of related infectious diseases.

Hepatocyte-derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis.

Liver fibrosis is characterized by the activation and transformation of hepatic stellate cells (HSCs) induced by various injury factors. The degree of liver fibrosis can be significantly improved, but persistent injury factors present a significant therapeutic challenge. Hepatocytes are the most important parenchymal cell type in the liver. In this study, we explored the molecular mechanisms by which damaged liver cells activate HSCs through extracellular vesicles. We established a coculture model of LO2 and LX2 and validated its exosomal transmission activity. Subsequently, differentially expressed long noncoding RNAs (lncRNAs) were screened through RNA sequencing and their mechanisms of action as competing endogenous RNAs (ceRNAs) further confirmed using biological methods, such as FISH and luciferase assays. Damaged liver cells induced activation of LX2 and upregulation of liver fibrosis-related markers. Exosomes extracted and identified from the supernatant fraction contained differentially expressed lncRNA cytoskeleton regulator RNA (CYTOR) that competed with microRNA-125 (miR-125) for binding to glial cell line-derived neurotrophic factor (GDNF) in HSCs, in turn, promoting LX2 activation. MiR-125 could target and regulate both CYTOR and GDNF and vice versa, as verified using the luciferase assay. In an in vivo model, damaged liver extracellular vesicles induced the formation of liver fibrosis. Notably, downregulation of CYTOR within extracellular vesicles effectively inhibited liver fibrosis. The lncRNA CYTOR in exosomes of damaged liver cells is upregulated and modulates the expression of downstream GDNF through activity as a ceRNA, providing an effective mechanism for activation of HSCs.

lncRNA CYTOR promotes lung adenocarcinoma gemcitabine resistance and epithelial-mesenchymal transition by sponging miR-125a-5p and upregulating ANLN and RRM2.

Lung adenocarcinoma (LUAD) is one of the most aggressive types of lung cancer. The prognosis of LUAD patients remains poor, and the overall efficacy of gemcitabine-based chemotherapy is still unsatisfactory. Long noncoding RNAs (lncRNAs) play important roles in several cancer types by interacting with multiple proteins, RNA, and DNA. However, the relationship between lncRNA dysregulation and gemcitabine resistance in LUAD has not been fully elucidated. In this study, lncRNA CYTOR expression and its association with the prognosis of LUAD patients are assessed by quantitative RT-PCR and Kaplan-Meier survival analysis. In vitro and in vivo functional studies are conducted to evaluate the biological functions of CYTOR in LUAD. The underlying mechanism regarding the tumor-promoting effects of CYTOR is explored using RNA immunoprecipitation, biotin-labelled RNA pulldown, luciferase reporter assays, and western blot analysis. We identify that CYTOR is an oncogenic lncRNA and is apparently upregulated in LUAD by analysing TCGA-LUAD data. High CYTOR expression is a poor prognostic factor for LUAD. Functional studies reveal that CYTOR confers LUAD cells with stronger resistance to gemcitabine treatment and upregulates the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. Mechanically, CYTOR acts as a competitive endogenous RNA (ceRNA) to absorb miR-125a-5p, weakens the antitumor function of miR-125a-5p, and ultimately upregulates ANLN and RRM2 expressions. Taken together, this study explains the mechanism of lncRNA in the gemcitabine resistance of LUAD and formulates a theoretical framework for the in depth study of LUAD.

CYTOR Facilitates Formation of FOSL1 Phase Separation and Super Enhancers to Drive Metastasis of Tumor Budding Cells in Head and Neck Squamous Cell Carcinoma.

Tumor budding (TB) is a small tumor cell cluster with highly aggressive behavior located ahead of the invasive tumor front. However, the molecular and biological characteristics of TB and the regulatory mechanisms governing TB phenotypes remain unclear. This study reveals that TB exhibits a particular dynamic gene signature with stemness and partial epithelial-mesenchymal transition (p-EMT). Importantly, nuclear expression of CYTOR is identified to be the key regulator governing stemness and the p-EMT phenotype of TB cells, and targeting CYTOR significantly inhibits TB formation, tumor growth and lymph node metastasis in head and neck squamous cell carcinoma (HNSCC). Mechanistically, CYTOR promotes tumorigenicity and metastasis of TB cells by facilitating the formation of FOSL1 phase-separated condensates to establish FOSL1-dependent super enhancers (SEs). Depletion of CYTOR leads to the disruption of FOSL1-dependent SEs, which results in the inactivation of cancer stemness and pro-metastatic genes. In turn, activation of FOSL1 promotes the transcription of CYTOR. These findings indicate that CYTOR is a super-lncRNA that controls the stemness and metastasis of TB cells through facilitating the formation of FOSL1 phase separation and SEs, which may be an attractive target for therapeutic interventions in HNSCC.

Long Non-coding RNA LINC00152 Requires EZH2 to Promote Mesothelioma Cell Proliferation, Migration, and Invasion.

BACKGROUND/AIM: Long non-coding RNAs (lncRNAs) establish gene regulatory networks in different human cancers and are involved in tumorigenesis. lncRNA LINC00152 is over-expressed in several malignant tumors and involved in tumorigenesis; however, its underlying regulatory mechanisms remain unclear. Mesothelioma, a cancer originating from mesothelial cells, is highly aggressive with a poor prognosis. Therefore, identification of new therapeutic targets is necessary for mesothelioma treatment. MATERIALS AND METHODS: Here, we conducted bioinformatics analyses of LINC00152 and enhancer of zeste homolog 2 (EZH2) expression levels and their correlation with the prognosis of patients with mesothelioma. Small interfering RNAs targeting LINC00152 and EZH2 were transfected into mesothelioma cell lines to analyze their biological functions and regulatory mechanisms. RESULTS: High LINC00152 expression was associated with a poor prognosis of patients with mesothelioma. LINC00152 knockdown inhibited the proliferation, migration, and invasion of mesothelioma cell lines. These results suggest that LINC00152 is a tumor-promoting factor in mesothelioma. EZH2 is highly expressed in mesothelioma and other malignancies. Direct interaction between LINC00152 and EZH2 is associated with cancer development and progression. When EZH2 expression was suppressed, LINC00152 knockdown did not suppress the proliferation, migration, and invasion of mesothelioma cells. Therefore, the tumor-promoting effect of LINC00152 in mesothelioma was dependent on EZH2 expression. CONCLUSION: LINC00152 promotes mesothelioma cell proliferation, migration, and invasion in cooperation with EZH2, highlighting its potential as an effective therapeutic target for mesothelioma.

Expression Level of lncRNA CYTOR in Iranian Cervical Cancer Patients.

Background: A critical role has been known for lncRNAs in the initiation and development of cancers. Therefore, lncRNAs have been reported as the possible biomarkers in relation to the diagnosis and therapy of malignancies. This project examined the change in CYTOR lncRNA expression in human cervical cancer samples as compared with adjacent healthy ones. Methods: We provided one hundred fifteen pairs of tumorous and adjacent healthy tissue specimens of cervical cancer patients. RNAs were isolated from tissue specimens and cDNAs were synthesized. We considered quantitative Real-time PCR (qRT-PCR) to examine the expression levels of CYTOR lncRNA. In addition, the biomarker activity of CYTOR and the associations between the lncRNA and clinicopathological characteristics were evaluated. Results: The significant increased expression of CYTOR was obtained in cancerous samples as compared with non-cancerous ones (P< 0.0001). A significant correlation was indicated between CYTOR expression and the squamous subtype of cervical cancer (p=0.046). The receiver operating characteristic (ROC) curve-related AUC (area under the curve), specificity, and sensitivity were calculated 0.88, 81.74%, and 80%, respectively, which may introduce CYTOR as a potential biomarker. Conclusion: CYTOR may be an effective oncogene and biomarker in cervical cancer cases given its increased expression in human cervical cancer tissues.

Expression analysis of cytoskeleton regulator RNA and Cyclin Dependent Kinase Inhibitor 2B genes in breast cancer.

BACKGROUND: Breast cancer has been found to be associated with deregulation of several non-coding genes and mRNA coding genes. OBJECTIVE: To assess expressions of CYTOR and CDKN2B in breast cancer and adjacent samples and find their relevance with clinical data. METHODS: We enumerated expression level of CDKN2B and CYTOR in 43 newly diagnosed breast cancer samples and their adjacent specimens using real-time PCR method Expression data was judged using Wilcoxon matched-pairs signed rank test. RESULTS: CYTOR level was higher in tumors compared with adjacent tissues. Nevertheless, there was no difference in expression of CDKN2B between these two sets of tissues. ROC curve analysis showed that CYTOR levels can differentiate between tumoral and adjacent tissues with AUC, specificity and sensitivity values of 0.65, 37% and 92% (P= 0.017). There was a positive correlation between expression levels of CYTOR and CDKN2B genes in breast cancer tissues (r= 0.5 and P= 0.0008) as well as adjacent tissues (r= 0.79 and P< 0.0001). Relative expression level of CDKN2B in normal tissues was associated with clinical stage (P= 0.014). Moreover, relative expression level of CDKN2B in tumor tissues was associated with the body weight. There was no other association between expressions of CYTOR and CDKN2B and clinical or pathological variables. CONCLUSIONS: Cumulatively, this study offers evidence for involvement of these genes in the pathoetiology of breast cancer.

lncRNA cytoskeleton regulator RNA (CYTOR): Diverse functions in metabolism, inflammation and tumorigenesis, and potential applications in precision oncology.

Long non-coding RNAs (lncRNAs) are a novel class of non-coding RNA (ncRNA), that have been studied extensively in the field of tumor research in recent years. In the case of tumor-associated lncRNAs, lncRNA cytoskeleton regulator RNA (CYTOR) displays extensive functions in tumorigenesis, including invasion, metastasis, malignant proliferation, glycolysis, and inflammatory response. Moreover, the dysregulation of CYTOR is closely related to clinicopathological characteristics, such as tumor stage, lymph node metastasis and infiltration, and poor prognosis of tumor patients. In this review, we provide a novel strategy to summarize the biological functions and clinical value of CYTOR in tumors through an overview of the literature combined with gene set enrichment analysis. A deeper understanding of the role of CYTOR in tumorigenesis may provide new diagnostic, prognostic and therapeutic markers for human tumors.

Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer.

Background: Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported. Methods: Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU-BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo. Results: The results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1)/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy. Conclusions: These results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.

CYTOR Promotes Proliferation of Lung Cancer Cell by Targeting miR-103a-3p to Upregulate HMGB1.

Lung cancer is one of the most dangerous malignant tumors to human health in the world. Previous researches have shown that cytoskeleton regulator RNA (CYTOR), a long noncoding RNA was involved in the occurrence and development of various types of cancer. The aim of this study is to investigate the clinical significance and biological function of CYTOR in lung cancer. Real-time quantitative PCR was applied to detect the expression of CYTOR. The proliferation of A549 and H1299 cells was analyzed by CCK8 assay. The luciferase reporter assay and RNA pull-down assay were used to reveal the interactions between CYTOR and its downstream targets. Western blot was used to detect the expression of high-mobility group protein B1 (HMGB1). Here we found CYTOR was upregulated in lung cancer tissues and cell lines. The proliferation of A549 and H1299 cells was inhibited after CYTOR silencing. In addition, CYTOR could directly interact with and negatively regulate miR-103a-3p, and miR-103a-3p inhibited cell proliferation by targeting HMGB1. The CYTOR/miR-103a-3p/HMGB1 axis promoted lung cancer cell proliferation. CYTOR sponges miR-103a-3p to promote the proliferation of lung cancer cells through HMGB1. The CYTOR/miR-103a-3p/HMGB1 axis plays a critical role in the progression of lung cancer.

Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation.

Background/Aims: The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. Methods: The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosis-related proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. Results: CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells. miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. Conclusions: CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

Research progress on regulatory mechanism of long non-coding RNA CYTOR in human cancer / 中国药理学通报

Cancer is difficult to cure because of its heterogeneity, drug resistance and easy recurrence and metastasis. Revealing the molecular mechanism of cancer genesis and development, identifying new diagnostic markers and molecular therapeutic targets are undoubtedly effective strategies to solve the problems of early diagnosis, treatment and improvement of prognosis of cancer patients. More and more studies have shown that long non-coding RNA (IncRNA) is specifically expressed in human cancer and is a key regulator of cancer occurrence and development. Cytoskeleton regulator RNA (CYTOR) is a carcinogenic lncRNA found in recent years. CYTOR is highly expressed in many types of cancer and regulates the development of cancer through a variety of pathways, which may be an effective biomarker for early cancer diagnosis, molecular targeted therapy and prognosis assessment. This paper reviews the molecular regulatory mechanism and related biological characteristics of CYTOR in human cancer, in order to provide new scientific reference for clinical cancer diagnosis and treatment.

ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT.

The glycolytic enzyme enolase 2 (ENO2) is dysregulated in many types of cancer. However, the roles and detailed molecular mechanism of ENO2 in colorectal cancer (CRC) metastasis remain unclear. Here, we performed a comprehensive analysis of ENO2 expression in 184 local CRC samples and samples from the TCGA and GEO databases and found that ENO2 upregulation in CRC samples was negatively associated with prognosis. By knocking down and overexpressing ENO2, we found that ENO2 promoted CRC cell migration and invasion, which is dependent on its interaction with the long noncoding RNA (lncRNA) CYTOR, but did not depend on glycolysis regulation. Furthermore, CYTOR mediated ENO2 binding to large tumor suppressor 1 (LATS1) and competitively inhibited the phosphorylation of Yes-associated protein 1 (YAP1), which ultimately triggered epithelial-mesenchymal transition (EMT). Collectively, these findings highlight the molecular mechanism of the ENO2-CYTOR interaction, and ENO2 could be considered a potential therapeutic target for CRC.

Long non-coding RNA CYTOR modulates cancer progression through miR-136-5p/MAT2B axis in renal cell carcinoma.

BACKGROUND: To explore the role of long noncoding RNAs (lncRNAs) cytoskeleton regulator RNA (CYTOR) in renal cell carcinoma (RCC). METHODS: The levels of CYTOR in RCC tissues and cell lines were detected by RT-qPCR. 786-O and Caki-1 cells were transfected with CYTOR-shRNA or pcDNA-CYTOR respectively, or co-transfected with CYTOR-shRNA and miR-136-5p inhibitor, or co-transfected with miR-136-5p mimic and pcDNA-MAT2B. MTT assay, Transwell assay and flow cytometry were used to evaluate cell proliferation, invasion and apoptosis. The relationship between lncRNA CYTOR and miRNA-136-5p was detected by dual luciferase reporter gene and RNA pull down assays, and the targeted relationship between miRNA-136-5p and MAT2B was verified by dual luciferase reporter gene assay. The interaction between MAT2B and BAG3 protein was verified by co-IP experiment. The role of lncRNA CYTOR in vivo was also examined. RESULTS: LncRNA CYTOR was up-regulated in RCC tissues and cell lines, and miR-136-5p was down-regulated in renal carcinoma cell lines and tissues. Downregulation of CYTOR inhibited cell proliferation and invasion and promoted apoptosis. miR-136-5p was sponged by lncRNA CYTOR, which negatively regulated the development of RCC. MAT2B was a target gene of miR-136-5p. MAT2B protein interacted directly with BAG3 protein to affect the proliferation, invasion and apoptosis of RCC cells. In vivo experiments showed that the expression level of miR-136-5p was increased, and MAT2B expression was decreased after CYTOR knockdown, thereby inhibiting the development of RCC. CONCLUSIONS: LncRNA CYTOR promoted the progression of RCC by targeting miR-136-5p to regulate the target gene MAT2B, which interacted with BAG3 protein.

Long non-coding RNA (lncRNA) CYTOR promotes hepatocellular carcinoma proliferation by targeting the microRNA-125a-5p/LASP1 axis.

This study investigated the function of long non-coding RNA (lncRNA) cytoskeleton regulator RNA (CYTOR) in hepatocellular carcinoma (HCC). In HCC, the expression of CYTOR and microRNA (miR)-125a-5p were measured by quantitative real-time PCR (qRT-PCR). The expression of actin skeletal protein 1 (LASP1) was evaluated by Western blot analysis. Flow cytometry assays, transwell assays, colony formation assay, and cell counting kit-8 (CCK-8) assay were used to evaluate the roles of miR-125a-5p and CYTOR in HCC cells. The target genes of CYTOR and miR-125a-5p were identified by bioinformatics analysis and Luciferase assay. CYTOR was upregulated in HCC cell lines, and knockdown of CYTOR inhibited HCC cell growth. MiR-125a-5p was downregulated in HCC cells and a target of CYTOR in regulating HCC progression. Furthermore, LASP1 was a downstream target of miR-125a-5p. Finally, CYTOR was found to be involved in HCC progression in vivo. CYTOR promotes HCC development by regulating the miR-125a-5p/LASP1 axis.

LncRNA CYTOR drives L-OHP resistance and facilitates the epithelial-mesenchymal transition of colon carcinoma cells via modulating miR-378a-5p/SERPINE1.

Long non-coding RNAs (lncRNAs) play a vital regulatory role in many human cancers. However, their underlying effect and molecular mechanism in chemoresistance need to be fully researched. This study found that lncRNA CYTOR expression was significantly up-regulated in colon carcinoma tissue and cells. Silencing lncRNA CYTOR in vitro facilitated L-OHP sensitivity of colon carcinoma cells and restrained epithelial-mesenchymal transition (EMT). Furthermore, lncRNA CYTOR could inhibit miR-378a-5p expression, while suppressing miR-378a-5p could attenuate the inhibition of lncRNA CYTOR silencing on L-OHP resistance and EMT. The downstream target mRNA of miR-378a-5p was further explored, and it was discovered that miR-378a-5p restrained SERPINE1 expression. Rescue assay indicated that overexpressing miR-378a-5p or silencing SERPINE1 expression counteracted the promotion of lncRNA CYTOR overexpression on L-OHP resistance and EMT of colon carcinoma cells. In vivo experiment exhibited that silencing lncRNA CYTOR repressed colon carcinoma growth, while miR-378a-5p inhibition diminished the suppression of silencing lncRNA CYTOR on colon carcinoma. These results testified that lncRNA CYTOR enhanced L-OHP drug resistance and induced EMT in colon carcinoma. It was also suggested that lncRNA CYTOR/miR-378a-5p/SERPINE1 axis was a regulatory pathway of L-OHP resistance in colon carcinoma. They could be potential therapeutic targets and prognostic biomarkers.Abbreviations: ATG: autophagy related; EPG: ectopic PGL granules; GFP: green fluorescent protein; LGG-1: LC3, GABARAP and GATE-16 family; LPLA-2: lysosomal phospholipase A2; PGL: P granule abnormality protein; PLA2: phospholipase A2; SD: standard deviation; SEPA-1: suppressor of ectopic P granules in autophagy mutant; SQST-1: sequestosome related.

Long noncoding RNA CYTOR triggers gastric cancer progression by targeting miR-103/RAB10.

Growing evidence has indicated that the long noncoding RNA (lncRNA) CYTOR is involved in the initiation and progression of malignancies, including gastric cancer. Nevertheless, the mechanisms of CYTOR in gastric cancer development are not fully understood. In the present study, we aimed to clarify the association of CYTOR, miR-103, and RAB10 in gastric cancer progression. We found that CYTOR expression was increased in metastatic gastric cancer biopsies compared with that in primary samples. CYTOR expression was significantly positively correlated with the invasiveness, lymph node metastasis, and advanced stages of gastric cancer. In addition, downregulation of CYTOR expression hampered cell proliferation and migration but induced cell apoptosis. Furthermore, CYTOR sponged miR-103 and diminished miR-103 expression, thus rescuing oncogene RAB10 expression. Knockdown of CYTOR suppressed tumor growth in human BGC823 mouse models. These findings suggest that the CYTOR/miR-103/RAB10 axis is a novel signaling pathway that facilitates gastric cancer progression. CYTOR-targeted interventions provide a rationale to improve therapies targeting gastric cancer progression.

MEG3 lncRNA is over-expressed in autism spectrum disorder.

Long non-coding RNAs (lncRNAs) comprise a group of regulatory transcripts which partake in the biological processes leading to development of neuropsychiatric disorders such as autism spectrum disorder (ASD). We measured circulatory levels of MEG3, GAS5, CYTOR, UCA1 lncRNAs and CRYBG3 gene in children with ASD and controls. Expression of MEG3 was remarkably higher in children with ASD when compared with controls (Posterior Beta = 2.919, SE = 0.51, P value < 0.0001). This difference was significant among male subgroups (Posterior Beta = 2.913, SE = 0.56, P value < 0.0001) as well as female subgroups (95% CrI for Beta = [0.29, 2.4], SE = 0.53, P value < 0.0001). Expression levels of other lncRNAs or CRYBG3 were not different between children with ASD and controls. Among children with ASD, the most robust correlations were found between GAS5/CYTOR, CYTOR/UCA1 and GAS5/UCA1 with correlation coefficients of 0.83, 0.83 and 0.73, respectively. Among controls, GAS5/UCA1, MEG3/UCA1 and GAS5/MEG3 pairs had the highest correlation coefficients (0.89, 0.84 and 0.80, respectively). ROC curve analysis revealed that MEG3 can distinguish children with ASD from controls with diagnostic power of 0.792 (P value < 0.0001). This value was higher among male subgroups (AUC = 0.84, P value < 0.0001) compared with female subgroups (AUC = 0.727, P value = 0.0727). The current research highlights the role of MEG3 in ASD and provides clues for depiction of an lncRNA network with possible contribution in the pathogenesis of ASD.