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MiR-135-5p inhibits TGF-?-induced epithelial-mesenchymal transition and metastasis by targeting SMAD3 in breast cancer.

ABSTRACT: Breast cancer (BC) is the most frequently diagnosed malignant tumors and the leading cause of death due to cancer in women around the world. A growing body of studies have documented that microRNA (miR)-135-5p is associated with the development and progression of BC. Considering that sekelsky mothers against dpp3 (SMAD3) plays a crucial role in transforming growth factor (TGF)-?/SMAD pathway and epithelial-mesenchymal transition (EMT) process, it is critical to elucidate the crosstalk and underlying regulatory mechanisms between miR-135-5p and SMAD3 in controlling TGF-?-mediated EMT in BC metastasis. Our results revealed a reciprocal expression pattern between miR-135-5p and SMAD3 mRNA in BC tissues and cell lines. Moreover, miR-135-5p was decreased in BC tissues compared to adjacent breast tissues; more interesting, miR-135-5p mRNA levels (Tumor/Normal, T/N) was further decreased in BC patients with lymph node metastasis, while SMAD3 mRNA levels were increased. Gain- and loss-of-function assays indicated that overexpression of miR-135-5p inhibited TGF-?-mediated EMT and BC metastasis in vitro and in vivo. Furthermore, knockdown of SMAD3 produced a consistent phenotype of miR-135-5p overexpression in breast cancer cells. Mechanistically, SMAD3, a pivotal transcriptional modulator of TGF-?/SMAD pathway, for the first time, was analyzed and identified as a target gene of miR-135-5p by bioinformatic algorithms and dual-luciferase reporter assays. Taken together, we clarified that miR-135-5p suppressed TGF-?-mediated EMT and BC metastasis by negatively regulating SMAD3 and TGF-?/SMAD signaling. Our findings supported that miR-135-5p may serve as a tumor suppressor, and be a valuable diagnostic biomarker for the treatment of BC.

SUBMITTER: Yang W

PROVIDER: S-EPMC7532519 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MiR-135-5p inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by targeting SMAD3 in breast cancer.

Yang Wen W Feng Wen W Wu Fenglei F Gao Yuan Y Sun Qian Q Hu Nan N Lu Wei W Zhou Jun J

Journal of Cancer 20200909 21

Breast cancer (BC) is the most frequently diagnosed malignant tumors and the leading cause of death due to cancer in women around the world. A growing body of studies have documented that microRNA (miR)-135-5p is associated with the development and progression of BC. Considering that sekelsky mothers against dpp3 (SMAD3) plays a crucial role in transforming growth factor (TGF)-β/SMAD pathway and epithelial-mesenchymal transition (EMT) process, it is critical to elucidate the crosstalk and underl ...[more]

PMID: 33033523

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Dataset Information

MiR-135-5p inhibits TGF-?-induced epithelial-mesenchymal transition and metastasis by targeting SMAD3 in breast cancer.

Publications

MiR-135-5p inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by targeting SMAD3 in breast cancer.

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