Research Paper Volume 13, Issue 17 pp 21435—21450
MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of non-small cell lung cancer cells
- 1 Department of Respiratory and Critical Care Medicine, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi’an 710018, Shaanxi, P.R. China
Received: August 25, 2020 Accepted: August 14, 2021 Published: September 9, 2021https://doi.org/10.18632/aging.203483
How to Cite
Copyright: © 2021 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Introduction: Non-small cell lung cancer (NSCLC) is the most common malignant tumor, and its recurrence and metastasis are the main causes of death. Recently, there is evidence that tumor derived exosomes play an important role in the occurrence and development of NSCLC.
Objective’s methods: First, the expression of miR-185-5p and RAB35 in NSCLC tissues, paracancerous tissues, NSCLC cell lines and normal human bronchial epithelial cell line was detected. Then, a series of gain-and loss-of-function assays were performed to validate the effects of miR-185-5p or RAB35 effects on A549 and H2170 cells proliferation, migration and invasion. Next, online bioinformatics analysis and luciferase reporter were used to predict and validate the targeting relationship of miR-185-5p and RAB35. Finally, tumor cell-derived exosomes with genetic downregulation of RAB35 or overexpression of miR-185-5p were co cultured with their parental cells to verify the regulatory role of RAB35 on exosome secretion and function.
Results: In NSCLC tissues and cell lines, miR-185-5p was downregulated, while RAB35 was significantly upregulated. Overexpression of miR-185-5p or knockdown of RAB35 expression inhibited cell proliferation, migration and invasion. Furthermore, we elucidated that RAB35 is a direct target of miR-185-5p. Additionally, exosomes derived from tumor cells restored cell proliferation, migration and invasion, whereas exosomes secreted by tumor cells with downregulation of RAB35 expression or overexpression of miR-185-5p lost their ability to restore cell proliferation, migration and invasion.
Conclusions: Our results demonstrate that miR-185-5p inhibits tumor cell-derived exosomes-mediated proliferation, migration and invasion of NSCLC cells by downregulating RAB35 expression.