Dataset Information

Drosha/Dicer/miR-7/TGF-β2 axis Sustained Acidic Microenvironment-induced Lung Metastasis

ABSTRACT: Extracellular pH (pHe) is lower in many tumors than in the corresponding normal tissue. Acidic tumor microenvironment has been shown to facilitate epithelial mesenchymal transition (EMT) and tumor metastasis, while the mechanisms underlying tumor acidic microenvironment-induced tumor cell metastasis remain undefined. Here, we aimed to investigate the tumor metastasis and the EMT by acidic microenvironment and to explore their mechanisms and clinical significance in lung cancer. Results showed that acidic pHe remarkably enhanced invasion ability of lung cells accompanying with increased mesenchymal and decreased epithelial markers. Moreover, acidic pHe triggered the inhibition of microRNA-7 (miR-7) expression and activation of TGF-β2/SMAD signaling. Mechanistic studies showed that TGF-β2 is a direct potential target gene of miR-7, and acidity-induced metastasis could be abolished by treatment with a TGFβRI inhibitor, anti-TGF-β2 antibody and miR-7 mimic, respectively. The clinical samples further revealed that miR-7 was decreased in lung tissues and antagonistically correlated with TGF-β2 expression, associating with overall survival and metastasis. In conclusion, our study indicated that acidic pHe showed enhanced invasive potential, and enhanced potential to develop experimental metastases by a novel mechanism involving tumor acidic microenvironment-induced regulation of miR-7/TGF-β2/SMAD axis. Our findings suggest that the possibility that pHe of the primary tumor may be an important prognostic parameter for lung cancer patients merit clinical investigation. Moreover, miR-7 may serve as prognostic molecular marker and a novel therapeutic target for lung cancer.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Linlin Lu

LAB HEAD: Linlin Lu

PROVIDER: PXD016524 | Pride | 2022-04-01

REPOSITORIES: Pride

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miR-7/TGF-<i>β2</i> axis sustains acidic tumor microenvironment-induced lung cancer metastasis.

Su Tao T Huang Suchao S Zhang Yanmin Y Guo Yajuan Y Zhang Shuwei S Guan Jiaji J Meng Mingjing M Liu Linxin L Wang Caiyan C Yu Dihua D Kwan Hiu-Yee HY Huang Zhiying Z Huang Qiuju Q Lai-Han Leung Elaine E Hu Ming M Wang Ying Y Liu Zhongqiu Z Lu Linlin L

Acta pharmaceutica Sinica. B 20210617 2

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic m ...[more]

PMID: 35251919

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