miR-185 influences Cdc42-N-WASP signaling pathway in gastric cancer by targeting CTTN.

Authors

Da Lian, Chengyao Bai, Xiaomeng Zhang, Xia Hou, Qingtian Wu, Pengyu Xie

Published in

Pakistan journal of pharmaceutical sciences. Volume 39. Issue 11. Pages 3351-3366. Nov 01, 2026.

Abstract

miR-185 expression is dysregulated in various tumors, but its role in gastric cancer remains unclear.
To investigate miR-185 expression and clinical significance in gastric cancer, explore its effects on malignant phenotypes and preliminarily elucidate the underlying mechanism.
Real-time polymerase chain reaction (PCR) was used to detect miR-185 expression in 58 archived gastric cancer tissue samples and paired adjacent normal tissues obtained from a hospital biospecimen repository. In SGC-7901 and AGS cells, the effects of miR-185 modulation on proliferation, apoptosis, epithelial-mesenchymal transition (EMT) and the cell division cycle protein 42 (Cdc42)-neural Wiskott-Aldrich syndrome protein (N-WASP) pathway were assessed using 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, Western blot and dual-luciferase reporter assay.
miR-185 expression was significantly downregulated in gastric cancer tissues and correlated with lymph node metastasis and advanced stage. In vitro, miR-185 overexpression inhibited proliferation, induced apoptosis, increased E-cadherin expression and decreased Vimentin, N-cadherin, Snail, Cdc42 and neural WASP expression. A dual-luciferase reporter assay confirmed that cortactin (CTTN) is a direct target of miR-185. These findings were consistent in both cell lines.
miR-185 is downregulated in gastric cancer and its low expression correlates with lymph node metastasis and advanced TNM stage. In vitro experiments indicate that upregulation of miR-185 suppresses gastric cancer cell proliferation, induces apoptosis and reverses epithelial-mesenchymal transition, possibly by targeting CTTN and thereby affecting Cdc42 and N-WASP expression. This single-center, small-sample (n=58) in vitro study lacks in vivo validation; the findings require confirmation in larger, multicenter cohorts. Nevertheless, this study provides the first experimental evidence for the miR-185/CTTN/Cdc42-N-WASP axis in gastric cancer.

PMID:
42632930
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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