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【Objective】 To investigate the expression profile of circRNA in nuclear receptor NURR1 overexpressed prostate cancer (PCa) cells, so as to provide reference for revealing the mechanism of PCa progression. 【Methods】 The expression of NURR1 in PCa was analyzed with UALCAN and TNMplot. The distinct circRNAs in NURR1 overexpressed PCa cells were screened with RNA-sequencing. The functions and signal pathways of differentially expressed circRNA molecules were analyzed with GO and KEGG. 【Results】 The circ_0000915 was significantly downregulated in DU145, LNCaP and PC3 cells. In NURR1 overexpressed DU145 cells, circ_0005991 was up-regulated, while circ_0001460 and circ_0001315 were down-regulated. In NURR1 overexpressed LNCaP cells, circ_0040729 and circ_0000722 were significantly up-regulated. In NURR1 overexpressed PC3 cells, circ_0001577, circ_0000854 and circ_0018168 were up-regulated, while circ_013035, circ_0003028, circ_0082096 and circ_0005320 were down-regulated. KEGG analysis revealed that the differentially expressed circRNAs were significantly associated with dorsal/ventral neural tube patterns, protein folding chaperones, disordered domain specific binding, positive regulation of BMP signaling pathways, and neural tube patterning functions. 【Conclusion】 CircRNAs play an important role in NURR1 mediated PCa progression, but there are certain differences among different prostate cancer cell types. The regulatory mechanism between NURR1 and circ_0000915 in the progression of PCa needs further investigation.
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Objective To investigate the correlation between the expression of the activator of HSP90 ATPase-1(AHA1),lysyl oxidase like-2 protein(LOXL2)in osteosarcoma tissues with mRNA expression of invasion and metastasis genes and their clinical significance.Methods A total of 90 osteosarcoma patients diagnosed and treated in North China Medical and Health Group Fengfeng General Hospital from February 2016 to March 2017 were selected as the research object.The expression of AHA1 mRNA,LOXL2 mRNA and invasion and metastasis genes Wnt family member 9A(Wnt9a)mRNA,zinc finger E-box binding homologous box 1(ZEB1)mRNA,zinc finger E-box binding homologous box 1(ZEB2)mRNA,N-cadherin(N-cad)mRNA,and vimentin(Vim)mRNA in tissues were detected by real-time fluorescence quantitative PCR.Pearson correlation analysis was used for correlation analysis.The differences in expression of AHA1 mRNA and LOXL2 mRNA in osteosarcoma patients among different clinical characteristics were compared.Kaplan-Meier survival analysis was used to analyze the effect of AHA1 mRNA and LOXL2 mRNA on the prognosis of osteosarcoma patients.The prognostic factors of osteosarcoma patients were analyzed by univariate and multivariate COX regression.Results The expressions of AHA1 mRNA(3.16±0.59),LOXL2 mRNA(2.84±0.44)and invasion and metastasis genes[Wnt9a mRNA(3.23±0.42),ZEB1 mRNA(2.73±0.39),ZEB2 mRNA(2.52±0.56),N-cad mRNA(2.71±0.65)and Vim mRNA(2.81±0.73)]in osteosarcoma tissues were higher than those in paracancerous tissues(1.10±0.21,0.95±0.18,0.79±0.15,0.64±0.11,0.98±0.19,0.68±0.14,0.72±0.15),and the differences were statissically significant(t=31.206,37.716,51.903,48.931,24.706,28.964,26.605,all P<0.05).There was a significant positive correlation between AHA1 mRNA and LOXL2 mRNA expression in osteosarcoma(r=0.712,P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA were significantly positively correlated with the expressions of invasion and metastasis genes(Wnt9a,ZEB1,ZEB2,N-cad,and Vim mRNA)in tumor tissue of osteosarcoma group(r=0.504~0.720,all P<0.05).The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma tissues with Eneeking stage Ⅲ,soft tissue infiltration,and lung metastasis were higher than those in patients with Eneeking stage Ⅰ~Ⅱ,no soft tissue infiltration,and no lung metastasis,with significant differences(t=14.122~171.054,all P<0.05).The 5-year survival rates of patients in the AHA1 mRNA high expression group and low expression group were 36.36%(16/44)and 78.26%(36/46),respectively.The 5-year cumulative survival rate of patients in the AHA1 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=16.081,P<0.05).The 5-year survival rates of patients with high and low expression of LOXL2 mRNA were 34.88%(15/43)and 78.72%(37/47),respectively.The 5-year cumulative survival rate of patients in the LOXL2 mRNA high expression group was significantly lower than that in the low expression group(Log-rank χ2=15.880,P<0.05).Lung metastasis(OR=1.921,P<0.05),Eneeking stage Ⅲ(OR=1.906,P<0.05),AHA1 mRNA high expression(OR=1.405,P<0.05),and LOXL2 mRNA high expression(OR=1.733,P<0.05)were independent risk factors affecting the poor survival prognosis of osteosarcoma patients.Conclusion The expressions of AHA1 mRNA and LOXL2 mRNA in osteosarcoma were increased,and they were correlated with the expression of invasion and metastasis genes,indicating they may be independent risk factors affecting the poor survival and prognosis of osteosarcoma patients.
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ObjectiveTo investigate the effect and mechanism of pachymic acid (PA) in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA (0, 20, 40, 80, 160 μmol·L-1) on cell viability was detected by cell counting kit-8(CCK-8), and the dose of PA was selected for subsequent experiments. The effect of PA (0, 20, 40, 80 μmol·L-1) on cell proliferation was evaluated by colony formation assay. The effect of PA (0, 20, 40, 80 μmol·L-1) on cell adhesion ability was observed by cell adhesion assay. The effect of PA (0, 20, 40, and 80 μmol·L-1) on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA (0, 20, 40, 80 μmol·L-1) on cell motility was further observed and verified by high-content imaging technology. The effects of PA (0, 20, 40, 80 μmol·L-1) on the expression of matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinasas (TIMP) related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group, the PA groups showed decreased cell viability(P<0.01), with the half-maximal inhibitory concentration (IC50) of ACHN cells of 70.42 μmol·L-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group(P<0.01). Cell adhesion assay showed that compared with the blank group, the PA groups displayed reduced cell adhesion(P<0.01). Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group (P<0.05,P<0.01). Transwell invasion assay showed that compared with the blank group, the number of transmembrane cells in PA groups was reduced(P<0.01). High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group(P<0.01). The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased (P<0.01), and TIMP-1 protein expression increased (P<0.01) compared with those in the blank group. In addition, compared with the blank group, the PA groups showed decreased protein expression of Smad2 and Smad3 (P<0.01). ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.
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Pseudogenes were initially thought to have no function and were called by aliases, such as "junk genes." With the emergence of large-scale genomics projects and more and more experimental studies, pseudogenes have been shown to play an important role in the occurrence and development of solid tumors, especially playing an important regulatory role in the occurrence and develepment of liver cancer, such as regulating the proliferation, apoptosis, invasion, metastasis, and immunity of liver cancer cells. Recent studies showed that pseudogenes can act as regulators of oncogenes and tumor suppressors in hepatocellular carcinoma (HCC) and can thus serve as prognostic markers and even therapeutic targets for this cancer type. In this review, we systematically summarize the mechanisms and functions of different pseudogenes in HCC and present their future prospects as therapeutic targets.
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Metastasis is the main cause of cancer-related death. Growing evidence has shown that changes in glucose metabolism in nasopharyngeal carcinoma cells affect the invasion and metastasis of nasopharyngeal carcinoma through many pathways. This review summarizes the molecular mechanism underlying abnormal glucose metabolism in nasopharyngeal carcinoma cells and analyzes its relationship with the invasion and metastasis of nasopharyngeal carcinoma, including aerobic glycolysis, aerobic oxidation, and pentose phosphate pathway. The aim is to provide novel approaches using the relationships among glucose metabolism, invasion, and metastasis in the targeted therapy of nasopharyngeal carcinoma.
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Lactic acid, a widespread metabolite in the tumor microenvironment, is mainly produced by tumor cells that undergo aerobic glycolysis. Lactic acid is closely related to the occurrence and development of tumor. It not only serves as a substrate to supply energy to tumor cells, but also acts as a signaling molecule to activate multiple pathways to promote invasive and metastasis, angiogenesis and immune escape of tumor cells. In-depth research on the mechanism of action of lactic acid in the occurrence and development of tumor and related therapeutic progress will help to find drug targets for treatment of tumor and improve prognosis of patients.
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ObjectiveTo explore the effect of Xiao Xianxiongtang (XXXT) on the transforming growth factor (TGF)-β1-induced invasion, metastasis, and epithelial-mesenchymal transition (EMT) of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells (NFAT) was performed by CB-DOCK (http://clab.labshare.cn/cb-dock/). The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group, model group, 0.1 g·L-1 XXXT group, 0.2 g·L-1 XXXT group, and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer, MGC-803 cells were transfected with Wnt5a overexpression plasmid, and then the cells were classified into blank plasmid group, Wnt5a-OE group, blank plasmid + XXXT (0.4 g·L-1) group, and Wnt5a-OE + XXXT (0.4 g·L-1) group. Cell viability was determined by cell counting kit-8 (CCK-8) assay, cell invasion and migration ability by Transwell invasion assay and wound healing assay, expression of EMT-related proteins (E-cadherin, N-cadherin, Vimentin, Snail) and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins [Wnt5a, calcineurin (CaN), NFAT1, and p-NFAT1] by Western blot, and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT (0.1, 0.2, 0.4 g·L-1) significantly promoted the loss of MGC-803 cell viability (P<0.05,P<0.01). It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner (P<0.05, P<0.01). Moreover, it promoted the expression of E-cadherin while suppressed the expression of N-cadherin, Vimentin, and Snail (P<0.05, P<0.01). Further experiments showed that XXXT could inhibit the expression of Wnt5a, CaN, NFAT1, and p-NFAT1, and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1, so as to reduce the cellular Ca2+ concentration (P<0.05, P<0.01). XXXT can reverse the effect of Wnt5a (P<0.05, P<0.01). ConclusionXXXT can attenuate the invasion, metastasis, and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway, thereby weakening the tumor-promoting effect of TGF-β1. In summary, XXXT may exert therapeutic effect on gastric cancer by regulating the invasion, metastasis, and EMT of gastric cancer cells.
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Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.
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Humans , 3' Untranslated Regions , China , Integrin alpha6/genetics , MicroRNAs/genetics , Stomach Neoplasms/pathologyABSTRACT
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck region. NPC has the characteristics of insidious onset, strong invasiveness and early lymph node metastasis. A variety of signaling pathways play a role in the invasion and metastasis of nasopharyngeal carcinoma, but the specific mechanism has not yet been fully elucidated. Recent studies have found that DNA methylation of nasopharyngeal carcinoma-related genes can affect the invasion and metastasis of nasopharyngeal carcinoma through a variety of signaling pathways including Wnt/β-catenin, PI3K/AKT and MAPK signaling pathways. This article reviews the specific mechanism of DNA methylation affecting the invasion and metastasis of nasopharyngeal carcinoma through the above-mentioned signaling pathways.
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Objective To explore the expression of miR-101-3p in gastric cancer and its mechanism on the invasion, metastasis, and angiogenesis of gastric cancer cells by targeting the STC-1 gene to regulate the PI3K/AKT signaling pathway. Methods qRT-PCR was used to detect the expression of miR-101-3p and STC-1 mRNA in gastric cancer tissues and BGC-823 cell and analyze the relationship between miR-101-3p expression and patients' clinical pathological factors. The cells were transfected with miRNA mimics and plasmids separately or in combination with LipofectamineTM 2000. TargetScanHuman prediction and dual-luciferase assay were used to verify the targeted regulation of miR-101-3p on STC-1. The effect and possible mechanism of miR-101-3p targeting the STC-1 gene on the invasion, metastasis, and angiogenesis of cancer cells were verified by scratch test, Transwell chamber test, Matrigel in vitro tube forming test, and Western blot assay. The development of the transplanted tumor was detected by nude mouse tumorigenicity test. Results The expression of STC-1 in gastric cancer tissues was higher than that in normal tissues. Compared with normal gastric tissues and GES-1 cells, miR-101-3p was down-regulated, and STC-1 mRNA was up-regulated in gastric cancer tissues and BGC-823 cell. The level of miR-101-3p was negatively correlated with the level of STC-1, and significantly correlated with the degree of tumor differentiation, TNM stage, and lymph node metastasis (P < 0.05). miR-101-3p directly targeted STC-1. The overexpression of miR-101-3p inhibited STC-1 expression and downregulated the expression of p-PI3K/PI3K, p-AKT/AKT, MMP-2, MMP-9, VEGF, and Ang2, consequently, inhibited tumor cell invasion, metastasis, and angiogenesis and reduced the size and weight of the transplanted tumors (P < 0.05). Conclusion miR-101-3p is down-regulated in gastric cancer and can target the STC-1 gene to regulate the PI3K/AKT signaling pathway and inhibit the invasion, metastasis, and angiogenesis of BGC-823 gastric cancer cells and the development of transplanted tumors in vivo.
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Endoplasmic reticulum (ER) is an important organelle responsible for protein, steroid, lipid and carbohydrate synthesis and calcium-dependent signal transduction in eukaryotic cells. ER homeostasis is essential for normal cell function. ER homeostasis imbalance can induce ER stress (ERS), which participates in the occurrence and development of diseases of the digestive system, respiratory system, circulatory system, nervous system, reproductive system, and endocrine system, and affects body health. Among various diseases, cancers seriously endanger people′s health due to its high mortality rate, disability rate, and recurrence rate. Due to the survival characteristics of unlimited proliferation, tumor cells are often exposed to various internal and external stimuli such as hypoxia, ischemia, excessive proliferation, and starvation, which destroy intracellular protein balance and induce ERS to some extent for survival. ERS plays a major role in various tumors and has dual functions in the survival of tumor cells: promoting the survival of tumor cells by activating a series of adaptive responses, while inducing ERS-related apoptosis pathways, so as to promote tumor cell death and inhibit tumor growth and invasion. As multiple functions of ERS in tumors are reported, many scholars have tried to intervene in the progress of tumors from the perspective of ERS. The therapeutic effect of traditional Chinese medicine (TCM) on tumors has been widely recognized. TCM can participate in the regulation of tumors from many aspects, including ERS, chemoradiotherapy resistance, gastrointestinal adverse reactions caused by chemotherapy, postoperative recurrence and metastasis. Since there are few reports on the antitumor effect of TCM from the perspective of ERS, this paper expounds the influence of ERS on tumorigenesis and development and the progress of TCM intervention in tumor through ERS, in order to provide a new direction for tumor treatment.
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Objective:To explore the molecular mechanism of spleen-strengthening traditional Chinese medicine (TCM) Weichang'an granule in inhibiting the invasion and metastasis of human gastric cancer MKN45 cells. Method:MKN45 cells were cultured <italic>in vitro</italic> and incubated with different concentrations(600, 900, 1 200, 1 500 mg·L<sup>-1</sup>)of Weichang'an granule for 24, 48, 72 h. Cell counting kit-8 (CCK-8) assay was used to detect its effect on the cell proliferation. Western blot was used to detect the expression of RUN and FYVE domain containing 3(RUFY3) in normal gastric mucosa cells and different gastric cancer cell lines. The expression of RUFY3 in the gastric cancer cells after Weichang'an granule intervention (600, 900, 1 200 mg·L<sup>-1</sup>) was detected by Western blot. Lentivirus transfection technique was used to achieve the stable and silenced expression of RUFY3 in gastric cancer MKN45 cells. Transwell assay was used to evaluate the influence of Weichang'an granule and silenced RUFY3 on the metastasis and invasion ability of MKN45. E-cadherin,N-cadherin,Vimentin,Zinc-finger transcription factor (SNAIL1 and SNAIL2) protein expression levels were detected by Western blot. Result:RUFY3 expression in human gastric cancer cells was significantly higher than that in normal gastric mucosa.The protein expression of RUFY3 in MKN45 cells of silenced RUFY3 group was significantly lower than that in Lentivirus negative group (<italic>P</italic><0.01). Weichang'an granule inhibited the expression of RUFY3 in human MKN45 gastric cancer cells (<italic>P</italic><0.05, <italic>P</italic><0.01) in a concentration-dependent manner. As compared with the blank group, both Weichang'an granule and silenced RUFY3 inhibited the metastasis and invasion ability of MKN45 (<italic>P</italic><0.01). After Weichang'an granule and silenced RUFY3 treatment, the protein expression of epithelial marker gene E-cadherin was up-regulated (<italic>P</italic><0.01), the protein expression of Vimentin and N-cadherin decreased, but with no statistical difference,while SNAIL1 and SNAIL2 were both significantly down-regulated (<italic>P</italic><0.01). Conclusion:By targeting RUFY3 to regulate epithelial mesenchymal transformation, the spleen-strengthening TCM compound Weichang'an granule can inhibit the invasion and metastasis of gastric cancer.
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In the process of tumor growth, with the proliferation and expansion of cancer cells, the reconstruction of extracellular matrix (ECM) of cancer tissues, the restriction of surrounding tissues and the flow of cancer tissue interstitial fluid, the special stress environment is formed in the tumor tissues. Significant differences are found in the mechanical environment and mechanical characteristics of different regions of tumor tissues, that is, mechanical heterogeneity. The reseach shows that the mechanical properties of tumor tissue invasion frontier areas are more significant and complex. In particular, the epithelial-mesenchymal transition (EMT) of tumor cells also prefers to concentrate on this area. The mechanical stress generated by the invasion front can induce EMT of tumor cells through TWIST1, TGF-β, WNT and other force signal transduction pathways, and promote tumor cell invasion. From the perspective of tumor biomechanics, this review focuses on the relationship between mechanical heterogeneity of tumor cells and EMT, so as to provide the theoretical basis for mechanoenvironment-targeted therapy of tumors.
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Flavonoids baicalin is the main bioactive component extracted from Scutellaria baicalensis Georgi. Baicalin has high medicinal value and shows extensive pharmacological effects including antitumor, antibiosis, anti-inflammatory, antioxidation, neuro-protection, and significant potential in tumor treatment. Recent studies have shown that baicalin suppresses the growth of many kinds of human cancer. The underlying mechanisms include induction of apoptosis, induction of cell cycle arrest, inhibition of tumor metastasis, suppression of angiogenesis, and so on. This article reviewed the research progress of baicalin on its antitumor pharmacology and possible mechanisms at home and abroad, and provided the basis for its further research.
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BACKGROUND@#MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression, influence cellular processes, and promote disease development. Variations in miRNA expression have been observed in many diseases, including hepatitis, cardiovascular disease, and cancer. The aim of this study is to investigate the effect of miR-144-3p on the invasion and metastasis of lung adenocarcinoma by targeting recombinant insulin receptor substrate 1 (IRS1).@*METHODS@#The expression of miR-144-3p in patients with lung adenocarcinoma was queried through bioinformatics database. MirTarPathway was used to analyze the KEGG enrichment pathway of miRNA. The expression and plasmid transfection efficiency of miR-144-3p in lung adenocarcinoma cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the changes of cell invasion and migration ability in different groups. Bioinformatics determined the key genes (Hub genes) of miR-144-3p; Double luciferase target assay was used to detect the mutual binding of miR-144 and IRS1. Western blot assay was used to detect the expression of IRS1 in different cell lines and the expression of after overexpression of miR-144.@*RESULTS@#The expression of miR-144-3p in lung adenocarcinoma tissues was decreased, qRT-PCR results indicated that the expression of miR-144-3p in lung adenocarcinoma cell A549 was significantly decreased (P<0.05), and the overexpressed plasmid was successfully transfected (P<0.05). Overexpression of miR-144 decreased the ability of cell migration and invasion (P<0.05). The expression of IRS1 was up-regulated in lung adenocarcinoma tissues. Survival analysis showed that patients with lung adenocarcinoma with high IRS1 expression had a poor prognosis (P<0.05). Double luciferase assay results showed that miR-144 could specifically identify 3'-UTR of IRS1 and inhibit reporter enzyme expression (P<0.05). Western blot indicated that the expression of IRS1 was increased in A549 cells (P<0.05). After overexpression of miR-144, the expression level of IRS1 protein was decreased (P<0.05). Transwell experiment proved that miR-144-3p could inhibit invasion and metastasis of lung adenocarcinoma cells by targeting IRS1 (P<0.05).@*CONCLUSIONS@#MiR-144-3p inhibits the invasion and migration of A549 cells through targeted regulation of IRS1, thus playing an anticancer role in tumors.
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Lupeol is a kind of triterpenoid widely found in a variety of Chinese herbal medicines and food-derived plants. It has multiple pharmacological activities such as antioxidant, anti-inflammatory and promoting skin healing. Recent studies have found that lupeol has anti-tumor effects on liver cancer, lung cancer, esophageal cancer and other tumor cells. The mechanisms of action are mainly by inhibiting tumor cell proliferation, inducing tumor cell apoptosis, and suppressing tumor cell invasion and metastasis. In this review, the anti-tumor research progress, pharmacological activities and molecular mechanisms of lupeol both in vitro and in vivo are reviewed and summarized to provide a theoretical basis for lupeol as a potential anti-tumor drug, and provide references for its anti-tumor mechanism.
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Objective To investigate the effects of miR-325-3p on the EMT, invasion and metastasis of gastric cancer cells by targeting CLDN1 gene. Methods We selected human gastric epithelial cell lines GES-1 and gastric cancer cell lines HGC27, SGC-7901, MKN-45 and MGC-803, and detected the expression of miR-325-3p and CLDN1. The targeting relation between miR-325-3p and CLDN1 were verified by dual luciferase report experiments, and the expression of miR-325-3p and CLDN1 in gastric cancer cells were intervened. qRT-PCR and Western blot were adopted to detect N-cadherin, vimentin and MMP2 expression in cells. CCK-8 assay, Transwell assay, flow cytometry were utilized to detect cell proliferation activity, invasion and apoptosis, respectively. Results Compared with GES-1 cells, miR-325-3p expression was decreased while CLDN1 expression was increased in MGC-803 cells (P < 0.05). CLDN1 was a target gene of miR-325-3p. Overexpression of miR-325-3p could inhibit the proliferation, invasion and EMT of gastric cancer cells, while promote the apoptosis of gastric cancer cells. However, the inhibition of miR-325-3p had the opposite effect (P < 0.05). The overexpression of CLDN1 could reverse the effect of miR-325-3p overexpression on the biological behavior of gastric cancer cells. Conclusion miR-325-3p can suppress CLDN1, inhibit the invasion, metastasis and EMT while promote the apoptosis of gastric cancer cells. miR-325-3p is expected to be a new target in gastric cancer treatment.
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Background: Matrix metalloproteinase-2 (MMP-2), which is supposed to enable cancer cells cross the basement membrane and metastasize by selectively cleaving type IV collagen, is anticipated to be a good diagnostic and prognostic marker in oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSMF). Thus, the study is aimed to estimate and compare the serum MMP-2 levels in patients with OSMF and OSCC.Methods: The study was conducted on 88 subjects, divided into three groups; Group I (healthy subjects, n=28), Group II (patients with OSMF, n=30), and Group III (patients with OSCC, n=30). Serum levels of MMP-2 were estimated and compared among the groups and further with the clinical parameters within the groups.Results: The mean serum MMP-2 levels in patients with OSMF (2.87±1.04 ng/mL) and with OSCC (11.55±2.16 ng/mL) were significantly higher than the healthy subjects (0.93±0.26 ng/mL) (p <0.0001, for both). Furthermore, the mean serum MMP-2 levels in OSMF subjects had a positive association with inter-incisal opening (IIO), however, there was no association with the degree of burning sensation. Likewise, in subjects with OSCC, levels of serum MMP-2 showed positive association with histopathological grades, however, significant association with the site of occurrence and primary tumor size was not found.Conclusions: Elevated serum MMP-2 levels can be used as a screening tool in the early detection of OSMF and OSCC cases. Moreover, MMP-2 might be a good marker in evaluating the tumor grade in OSCC and the IIO in OSMF.
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Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with an increasing incidence and mortality in recent years.Despite advanced improvements in its diagnosis and therapy,the prognosis for ICC patients remains poor.High heterogeneity and malignant biological behavior are the main factors determining the prognosis of ICC.An in-depth study of the mechanism of ICC invasion and metastasis is expected to help optimizing clinical decision-making.The application of advanced technologies such as next-generation sequencing has enhanced the researchers' understanding of heterogeneity of ICC and characteristics of invasion and metastasis.Studies have found that ICC gene expression abnormalities (gene mutations,fusion gene formation,and abnormalities in gene expression regulatory pathways) and microRNA expression disorders are closely related to ICC cell proliferation,invasion and metastasis.In addition,ICC is usually characterized by a dense desmoplastic stroma,in which cancer-associated myofibroblasts are the major cellular components and play an important role in inducing epithelial-mesenchymal transition,promoting malignant cell invasion and metastasis,and even accelerating ICC progression.
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Objective To investigate the mechanism via which artesunate regulates the invasion and metastasis of colon cancer cells and the expression of members of the TGF-β1/Smad4 signaling pathway. Methods The cell counting kit 8 (CCK8), nude mouse xenograft model, Transwell invasion assay, and flow cytometry were used to investigate the effect of artesunate on the invasion and metastasis of colon cancer cells. Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of TGF-β1 and Smad4 proteins and mRNA, respectively. Results Artesunate inhibited the growth of transplanted tumor, cell proliferation, and invasion and promoted apoptosis. It inhibited TGF-β1 expression and promoted Smad4 expression. TGF-β1 inhibitors reversed the inhibitory effect of artesunate. Conclusion Artesunate can inhibit the growth of xenograft tumor in nude mice and its mode of action may be related to the TGF-β1/Smad4 signaling pathway.