CHML targeted by miR-199a-3p promotes non-small cell lung cancer cell growth via binding to Rab5A.

Choroideremia-like (CHML) has been demonstrated to be related to the development of urothelial carcinoma, multiple myeloma, and hepatocellular carcinoma. Whereas, the association between CHML and lung cancer remains dimness. CHML expression was analyzed in NSCLC patients from TCGA dataset and evaluated in our collected NSCLC tissues and NSCLC cell lines. The effects of CHML on the proliferation and apoptosis of NSCLC were investigated in A549 and H1299 cells that downregulation of CHML as well as in H1299-induced xenograft mouse model. An upstream miRNA of CHML was further analyzed. Moreover, bioinformatics analysis and co-immunoprecipitation assay were carried out to explore the mechanism of CHML in NSCLC. We found CHML expression was upregulated in NSCLC patients and cell lines compared with their controls. Knockdown of CHML suppressed the viability and BrdU-positive cell number, and elevated the proportion of Tunel-positive cells and levels of Bax/Bcl-2 and cleaved-caspase-3 in NSCLC cells. In mouse models, downregulation of CHML decreased tumor volume and weight, attenuated Ki-67 staining, whereas elevated numbers of Tunel-positive cells, and upregulated levels of Bax/Bcl-2 and cleaved-caspase-3. CHML was demonstrated to be a target of miR-199a-3p. miR-199a-3p inhibitor significantly promoted the proliferation, and attenuated the apoptosis of H1299 cells, which were abrogated by CHML silencing. CHML promoted the proliferation of NSCLC cells via directly binding to Rab5A. Taken together, this study revealed that CHML was an oncogene in NSCLC and it could promote the proliferation and inhibit apoptosis of NSCLC cells through binding to Rab5A. CHML was targeted by miR-199a-3p in this cancer. Copyright © 2021 Elsevier GmbH. All rights reserved.

Citation

Changqing Dong, Hui Cao, Zhengcheng Liu, Lei Xi, Ye Shi, Rusong Yang. CHML targeted by miR-199a-3p promotes non-small cell lung cancer cell growth via binding to Rab5A. Pathology, research and practice. 2021 Nov;227:153626

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PMID: 34649053

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