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Published on: May 1, 2019
miR-135b-5p promotes gastric cancer progression by targeting CMTM3
Mingdong Lu1, Yingpeng Huang1, Weijian Sun2
1Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong, P.R. China.
Abstract:
CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is considered to be a tumor suppressor gene in multiple types of malignancies. Previous studies have indicated that CMTM3 suppresses metastasis and epithelial-mesenchymal transition (EMT) in gastric cancer. However, its role in gastric cancer cell proliferation has rarely been discussed. Moreover, the regulatory mechanisms of CMTM3 in gastric cancer remain unclear. In this study, RT‑qPCR and IHC were used to assess the expression of CMTM3 and miR‑135b‑5p in gastric cancer tissues and cell lines. We found that the expression of miR‑135b‑5p was negatively associated with CMTM3 in gastric cancer tissues, and we verified that miR‑135b‑5p directly targeted CMTM3 in gastric cancer cells by dual-luciferase reporter assay. CCK8 assay, Transwell assay and flow cytometric analysis were conducted to examine the functions of CMTM3 and miR‑135b‑5p in vitro. Our results demonstrated that the overexpression of CMTM3 or the suppression of miR‑135b‑5p using an inhibitor suppressed SGC‑7901 gastric cancer cell proliferation, invasion and cell cycle progression, and promoted SGC‑7901 cell apoptosis. Furthermore, a BALB/c nude mouse subcutaneous xenograft model was used to verify the function of miR‑135b‑5p and CMTM3. Our results revealed that miR‑135b‑5p inhibitor significantly suppressed SGC‑7901 cell tumorigenesis in vivo. In addition, IHC revealed that CMTM3 expression was markedly increased in tumors infected with miR‑135b‑5p inhibitor lentivirus. On the whole, the findings of the present study suggest that the overexpression of miR‑135b‑5p inhibits CMTM3 expression, and promotes gastric cancer progression and metastasis. Our findings provide a novel therapeutic target for gastric cancer.
Insights
MicroRNA-135b-5p promotes gastric cancer progression by inhibiting the tumor suppressor CMTM3. Suppressing miR-135b-5p or overexpressing CMTM3 could be a novel therapeutic strategy for gastric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) acts as a tumor suppressor gene, inhibiting metastasis and epithelial-mesenchymal transition (EMT) in gastric cancer.
- The specific role of CMTM3 in gastric cancer cell proliferation and its regulatory mechanisms remain largely undefined.
Purpose of the Study:
- To investigate the regulatory relationship between CMTM3 and miR-135b-5p in gastric cancer.
- To elucidate the functional impact of CMTM3 and miR-135b-5p on gastric cancer cell proliferation, invasion, and apoptosis.
- To validate the therapeutic potential of targeting this pathway in vivo.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) to assess gene expression.
- Dual-luciferase reporter assay to confirm direct targeting.
- In vitro assays including CCK8, Transwell, and flow cytometry.
- In vivo studies using a BALB/c nude mouse xenograft model.
Main Results:
- miR-135b-5p expression was negatively correlated with CMTM3 expression in gastric cancer tissues.
- miR-135b-5p directly targets and inhibits CMTM3 in gastric cancer cells.
- Overexpression of CMTM3 or inhibition of miR-135b-5p suppressed cancer cell proliferation, invasion, and cell cycle progression, while promoting apoptosis.
- In vivo, miR-135b-5p inhibition significantly reduced tumor growth and increased CMTM3 expression.
Conclusions:
- The miR-135b-5p/CMTM3 axis plays a critical role in regulating gastric cancer progression and metastasis.
- Overexpression of miR-135b-5p promotes gastric cancer by suppressing CMTM3.
- Targeting the miR-135b-5p/CMTM3 pathway offers a promising therapeutic strategy for gastric cancer treatment.
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