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miR-148a inhibits cell proliferation and migration through targeting ErbB3 in colorectal cancer
Wei Zhao1, Jianbao Zheng1, Guangbing Wei1
1Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Abstract:
Colorectal cancer is a common gastrointestinal cancer ranking in third place of all cancers. Downregulation of miR-148a has been observed in many tumors, and miR-148a was found to be an oncogene in colorectal cancer. The aim of our study was to investigate the molecular mechanisms by which miR-148a and ErbB3 proliferate and migrate in colorectal cancer. The expression of miR-148a and ErbB3 were measured by western blot analysis and RT-qPCR. MTT and transwell assays were performed to analyze the proliferative and migratory abilities. The dual luciferase reporter assay was employed to confirm miR-148a regulated the expression of ErbB3 in colorectal cancer. It was discovered that miR-148a was overexpressed while ErbB3 expression was low in colorectal cancer, and the mRNA level of miR-148a had a negative correlation with the expression of ErbB3. Upregulation of miR-148a suppressed the proliferation and migration in colorectal cancer cells. Furthermore, ErbB3 was identified as a direct target of miR-148a, which suppressed the proliferation and migration through directly binding to the 3'UTR of ErbB3 mRNA. This study established that miR-148a inhibited the proliferative and migratory abilities through mediating the expression of ErbB3. The newly identified miR-148a/ErbB3 axis provides novel insight into the pathogenesis of colorectal cancer, and represents a potential target for treatment of colorectal cancer.
Insights
MicroRNA-148a (miR-148a) suppresses colorectal cancer growth and spread by targeting ErbB3. This newly found miR-148a/ErbB3 pathway offers new insights into colorectal cancer development and potential treatments.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally.
- Downregulation of microRNA-148a (miR-148a) is implicated in various cancers, acting as an oncogene in CRC.
- The precise molecular mechanisms linking miR-148a and ErbB3 in CRC proliferation and migration remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the roles of miR-148a and ErbB3 in colorectal cancer proliferation and migration.
- To investigate the regulatory relationship between miR-148a and ErbB3 in CRC cells.
- To identify the miR-148a/ErbB3 axis as a potential therapeutic target for colorectal cancer.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and Western blot analysis to measure miR-148a and ErbB3 expression.
- MTT and Transwell assays to assess cell proliferation and migration.
- Dual-luciferase reporter assay to confirm direct targeting of ErbB3 by miR-148a.
Main Results:
- miR-148a was found to be overexpressed in colorectal cancer, with its mRNA levels negatively correlated with ErbB3 expression.
- Upregulation of miR-148a significantly suppressed proliferation and migration in colorectal cancer cells.
- ErbB3 was confirmed as a direct target of miR-148a, with miR-148a inhibiting CRC cell proliferation and migration by binding to the 3'UTR of ErbB3 mRNA.
Conclusions:
- miR-148a inhibits colorectal cancer cell proliferation and migration by directly targeting and downregulating ErbB3 expression.
- The identified miR-148a/ErbB3 signaling axis provides novel insights into colorectal cancer pathogenesis.
- This axis represents a promising therapeutic target for colorectal cancer treatment.
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