miR-135b-5p promotes gastric cancer progression by targeting CMTM3

Lu, Mingdong; Huang, Yueyue; Sun, Weijian; Li, Pihong; Li, Liyi; Li, Leping

doi:10.3892/ijo.2017.4222

Cited by 36 publications

(36 citation statements)

References 37 publications

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“…In non-small cell lung cancer, amplification of miR-135b suppressed the chemoresistance of cancer cells to cisplatin treatment by downregulating Frizzled-1 (55). However, opposite effects of miR-135b-5p in certain cancers have also been reported (56,57). This could be partially explained by the mechanism by which miRNA binding to mRNAs is often achieved with imperfect complementarity, and its targets varied in different cellular contexts and tumor types.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Integrin Subunit Alpha 2 by miR-135b-5p Modulates Chemoresistance in Gastric Cancer

et al. 2020

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Chemotherapy has substantially improved gastric cancer (GC) patient outcomes in the past decades. However, the development of chemotherapy resistance has become the major cause of treatment failure. Although numerous molecules have been implicated in GC chemoresistance, its pathological mechanisms are still unclear. Here, we found that integrin subunit alpha 2 (ITGA2) is upregulated in chemoresistant GC cells and that increased ITGA2 levels correlated with the poor prognosis of GC patients who received chemotherapy. ITGA2 overexpression led to elevated chemotherapy resistance and drug-induced apoptosis inhibition in GC cells. ITGA2 knockdown resulted in restored chemosensitivity and increased apoptosis in chemoresistant GC cells both in vitro and in vivo. NanoString analysis revealed a unique signature of deregulated pathway expression in GC cells after ITGA2 silencing. The MAPK/ERK pathway and epithelial-mesenchymal transition (EMT) were found to be downregulated after ITGA2 knockdown. miR-135b-5p was identified as a direct upstream regulator of ITGA2. miR-135b-5p overexpression reduced chemoresistance and induced apoptosis in GC cells and attenuated ITGA2-induced chemoresistance and antiapoptotic effects by inhibiting MAPK signaling and EMT. In conclusion, this study underscored the role and mechanism of ITGA2 in GC and suggested the novel miR-135b-5p/ITGA2 axis as an epigenetic cause of chemoresistance with diagnostic and therapeutic implications.

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Section: Discussionmentioning

confidence: 99%

Regulation of Integrin Subunit Alpha 2 by miR-135b-5p Modulates Chemoresistance in Gastric Cancer

et al. 2020

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“…For example, in human renal cell carcinoma (RCC), CMTM5 was significantly downregulated, and overexpression of CMTM5 efficiently suppressed the migration and invasion of RCC cells, and inhibited the cell growth of RCC cells by inducing cell cycle arrest at G0/G1 phase, which were indicated that CMTM5 functioned as a tumor suppressor in RCC cells . In gastric cancer, overexpression of CMTM3 suppressed cell proliferation, cell cycle progression and invasion, and promoted cell apoptosis, which also indicated that CMTM3 was a tumor suppressor gene in gastric cancer …”

Section: Discussionmentioning

confidence: 99%

“…18 In gastric cancer, overexpression of CMTM3 suppressed cell proliferation, cell cycle progression and invasion, and promoted cell apoptosis, which also indicated that CMTM3 was a tumor suppressor gene in gastric cancer. 22 CMTMs 6, 7, and 8 forms a gene cluster on 3p22, a chromosomal region rich in tumor-suppressor genes, whereas only CMTM7 has been shown to be downregulated or silenced in several malignancies, but its function and roles were still unknown in liver cancer. 5,10,23 Several studies have helped to elucidate the mechanisms of CMTM7 as a tumor suppressor, including those performed on EGFR internalization, AKT signaling pathway inhibition, and promoter methylation.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Huang

Yang

et al. 2019

The Kaohsiung J of Med Scie

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Chemokine‐like factor (CKLF)‐like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain‐containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin‐dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.

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“…Furthermore, some studies have suggested that miRNAs can function as important specific regulators in a number of biologic processes (7). The correlation between microRNA-135b (miR-135b) and the Laurén classification, tumor differentiation, invasion, and pathologic tumor-nodemetastasis stage of GC was outlined in a previous study (8). The overexpression of miR-135b has been found to be conducive to the chemoresistance of cells, while promoting the chemosensitivity of drug-resistant lung cancer cell lines (9).…”

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confidence: 99%

Poor expression of microRNA‐135b results in the inhibition of cisplatin resistance and proliferation and induces the apoptosis of gastric cancer cells through MST1‐mediated MAPK signaling pathway

Zhou

Chen

2018

FASEB j.

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Gastric cancer (GC) has been classified as the fourth leading cause of cancer‐related deaths worldwide. Due to their ability to suppress the expression of target genes, microRNAs (miRNAs) are listed as one of the key elements involved in the formation and development of tumors. This study was therefore conducted to investigate the effects of microRNA‐135b (miR‐135b) on cisplatin [ds‐diamminedichloroplatinum (CDDP)] resistance of GC cells through the MAPK signaling pathway by targeting mammalian ste20‐like kinase 1 (MST1). A microarray‐based gene expression analysis was performed to screen the GC‐related differentially expressed genes. The 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide assay was performed to determine the sensitivity of GC cells to CDDP. The bioinformatics database and dual lucif erase reporter gene assay were used to check whether MST1 was a direct target gene of miR‐135b. GC cell lines were prepared with high CDDP resistance, after which they were cultured and transfected respectively, followed by the administration of transfected cells into nude mice and subsequent treatment with CDDP in an attempt to identify the underlying mechanisms and functions of miR‐135b in relation to MST1 in GC progression. The results were highly indicative of the crucial role played by MST1 in the development of GC and the sensitivity of GC to CDDP. miR‐135b was found to regulate MST1, which in turn had an impact on the development of GC. MKN28 was observed to be most sensitive to CDDP, whereas MKN45 presented with the poorest sensitivity to CDDP. Furthermore, the down‐regulation of miR‐135b resulted in inactivation of the MAPK signaling pathway; increased the expression of MST1 and Bax; and decreased expression of p‐p38MAPK, p‐ERKl/2, P‐glycoprotein, p38MAPK, ERK1/2, multidrug resistance protein 1, multidrug resistance‐associated protein 1, lung resistance‐related protein, and Bcl‐2, thus inhibiting CDDP resistance of GC cells. The down‐regulation of miR‐135b also restrained cell proliferation and induced the apoptosis rate of GC cells. In summary, the results of this study showed that the down‐regulation of miR‐135b induced apoptosis, and it inhibited proliferation and CDDP resistance of GC cells by inactivating the MAPK signaling pathway and increasing the expression of MST1.—Zhou, J., Chen, Q. Poor expression of microRNA‐135b results in the inhibition of cisplatin resistance and proliferation and induces the apoptosis of gastric cancer cells through MST1‐mediated MAPK signaling pathway. FASEB J. 33, 3420–3436 (2019). http://www.fasebj.org

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miR-135b-5p promotes gastric cancer progression by targeting CMTM3

Cited by 36 publications

References 37 publications

Regulation of Integrin Subunit Alpha 2 by miR-135b-5p Modulates Chemoresistance in Gastric Cancer

Regulation of Integrin Subunit Alpha 2 by miR-135b-5p Modulates Chemoresistance in Gastric Cancer

Overexpression of CMTM7 inhibits cell growth and migration in liver cancer

Poor expression of microRNA‐135b results in the inhibition of cisplatin resistance and proliferation and induces the apoptosis of gastric cancer cells through MST1‐mediated MAPK signaling pathway

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