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MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric

Yanjun Qu¹, Haiyang Zhang¹, Jingjing Duan¹

¹Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.

|April 28, 2016

Abstract:

TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, we found that TGFBR2 protein levels were consistently upregulated in gastric cancer tissues, whereas TGFBR2 mRNA levels varied among these tissues, indicating that a post-transcriptional mechanism is involved in the regulation of TGFBR2. MiRNAs are known to regulate gene expression at the post-transcriptional level. Therefore, we performed bioinformatics analyses to search for miRNAs potentially targeting TGFBR2. MiR-17-5p was found to bind to the 3'UTR of TGFBR2 mRNA, and further validation of this specific binding was performed through a reporter assay. An inverse correlation between miR-17-5p and TGFBR2 protein was observed in gastric cancer tissues. Cell studies revealed that miR-17-5p negatively regulated TGFBR2 expression by directly binding to the 3'UTR of TGFBR2 mRNA, thereby promoting cell growth and migration. We also validated the role of TGFBR2 using siRNA and an overexpression plasmid. The results of our study suggest a novel regulatory network in gastric cancer mediated by miR-17-5p and TGFBR2 and may indicate that TGFBR2 could serve as a new therapeutic target in gastric cancer.

Insights

MicroRNA-17-5p (miR-17-5p) targets TGFBR2 in gastric cancer, promoting cell growth and migration. This discovery reveals a new regulatory network and a potential therapeutic target for gastric cancer treatment.

Area of Science:

Molecular Biology
Oncology
Gene Regulation

Background:

Transforming growth factor beta receptor 2 (TGFBR2) regulates the TGF-β signaling pathway, crucial in cell growth and invasion.
TGFBR2's role in gastric cancer progression is significant, but its precise regulatory mechanisms remain largely unknown.

Purpose of the Study:

To elucidate the post-transcriptional regulation of TGFBR2 in gastric cancer.
To identify specific microRNAs (miRNAs) targeting TGFBR2 and investigate their functional impact.

Main Methods:

Bioinformatic analysis to predict miRNA targets of TGFBR2.
Reporter assays to validate miRNA binding to the TGFBR2 3'UTR.
Correlation analysis of miR-17-5p and TGFBR2 protein levels in gastric cancer tissues.
In vitro cell studies using siRNA and overexpression plasmids to assess functional effects.

Main Results:

TGFBR2 protein was upregulated in gastric cancer, while mRNA levels varied, suggesting post-transcriptional control.
MiR-17-5p was identified as a direct binder to the TGFBR2 3'UTR.
An inverse correlation between miR-17-5p and TGFBR2 protein levels was observed.
MiR-17-5p negatively regulated TGFBR2 expression, promoting gastric cancer cell growth and migration.

Conclusions:

A novel regulatory network involving miR-17-5p and TGFBR2 in gastric cancer was identified.
MiR-17-5p acts as a tumor suppressor by downregulating TGFBR2.
TGFBR2 represents a potential therapeutic target for gastric cancer intervention.

Read full analysis

Keywords:

TGFBR2 cell proliferation gastric cancer miR-17-5p migration

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