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Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2
Lin Zhou1, Xin Liang2, Lingling Zhang2
1Department of Laboratory Medicine, Changzhen Hospital, Second Military Medical University, Shanghai 200003, China.
Abstract:
microRNA-27a (miR-27a) is frequently dysregulated in human carcinoma, including gastric cancer. The B-cell translocation gene 2 (BTG2) has been implicated in gastric carcinogenesis. However, till now, the link between miR-27a and BTG2 in gastric cancer has not been reported. Here, we found that two isoforms of mature miR-27a, miR-27a-5p and miR-27-3p, were both frequently overexpressed in gastric cancer tissues and cell lines, whereas the expression level of miR-27-3p in gastric cancer was significantly higher than that of miR-27a-5p. And overexpression of miR-27a-3p, but not miR-27a-5p, markedly promoted gastric cancer cell proliferation in vitro as well as tumor growth in vivo. Further experiments revealed that BTG2 was a direct and functional target of miR-27a-3p in gastric cancer and miR-27a-3p inhibition obviously up-regulated the expression of BTG2. In turn, overexpression of BTG2 triggered G1/S cell cycle arrest, induced subsequent apoptosis, and inhibited C-myc activation following Ras/MEK/ERK signaling pathway, which involved in the biological effects of miR-27a-3p/BTG2 axis on gastric carcinogenesis and cancer progression. Overall, these results suggested that the miR-27a-3p/BTG2 axis might represent a promising diagnostic biomarker for gastric cancer patients and could be a potential therapeutic target in the management of gastric cancer.
Insights
MicroRNA-27a-3p (miR-27a-3p) promotes gastric cancer by targeting B-cell translocation gene 2 (BTG2). This miR-27a-3p/BTG2 axis is a potential diagnostic biomarker and therapeutic target for gastric cancer.
Area of Science:
- Molecular biology
- Oncology
- Biochemistry
Background:
- MicroRNA-27a (miR-27a) is dysregulated in human cancers, including gastric cancer.
- B-cell translocation gene 2 (BTG2) plays a role in gastric carcinogenesis.
- The relationship between miR-27a and BTG2 in gastric cancer remains unexplored.
Purpose of the Study:
- To investigate the role of miR-27a isoforms in gastric cancer.
- To identify the target gene of miR-27a in gastric cancer.
- To elucidate the functional mechanism of the miR-27a/BTG2 axis in gastric carcinogenesis.
Main Methods:
- Quantitative real-time PCR to measure miR-27a and BTG2 expression.
- In vitro cell proliferation assays and in vivo tumor growth studies.
- Western blotting and luciferase reporter assays to confirm target interaction and pathway analysis.
Main Results:
- Both miR-27a-5p and miR-27a-3p were overexpressed in gastric cancer tissues and cell lines, with miR-27a-3p showing higher expression.
- Overexpression of miR-27a-3p promoted gastric cancer cell proliferation and tumor growth.
- BTG2 was identified as a direct target of miR-27a-3p; miR-27a-3p inhibition upregulated BTG2, which induced cell cycle arrest, apoptosis, and inhibited C-myc activation via the Ras/MEK/ERK pathway.
Conclusions:
- The miR-27a-3p/BTG2 axis plays a critical role in gastric carcinogenesis and progression.
- miR-27a-3p promotes gastric cancer by downregulating BTG2.
- The miR-27a-3p/BTG2 axis represents a potential diagnostic biomarker and therapeutic target for gastric cancer.
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