MiR-185-5p targets RAB35 gene to regulate tumor cell-derived exosomes-mediated proliferation, migration and invasion of non-small cell lung cancer cells

Abstract

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.

Development and Validation of a Machine Learning Prognostic Model of m5C Related immune Genes in Lung Adenocarcinoma

“… 33 Studies had demonstrated that hsa-miR-183-5p could inhibit the proliferation, migration and invasion of non-small cell lung cancer cells by down-regulating the expression of RAB35 and KLF7. 48 , 49 The 3 biomarkers (HLA-DMB, PPIA, GPI) were associated with hsa-miR-135a-5p and hsa-miR-183-5p, suggesting that these biomarkers have therapeutic potential for LUAD.…”

The Circular RNA circFGFR4 Facilitates Resistance to Anti-PD-1 of Triple-Negative Breast Cancer by Targeting the miR-185-5p/CXCR4 Axis

“…For example, miRNA-185-5p inhibits the proliferation, migration, and invasion of non-small cell lung cancer cells by targeting RAB35. 25 In glioma, circPOSTN promotes tumor progression by acting as a miR-185-5p sponge to upregulate KIF1B expression. 26 In TNBC, the expression of circRNA-CREIT was decreased in doxorubicin resistant TNBC cells and associated with a poor prognosis.…”

Exosomal hsa-miR-151a-3p and hsa-miR-877-5p are potential novel biomarkers for predicting bone metastasis in lung cancer

“…Recently, several dysregulated miRNAs are involved in the pathogenesis of lung cancer by affecting cell proliferation, apoptosis, migration, and metastasis [ 19 ]. Through genome-wide investigation and analysis, a set of miRNAs were found to be deregulated in the tissues of lung cancer patients with BM, and a group of miRNAs are closely correlated to prognosis and can be used as diagnostic biomarkers [ 20 , 21 ]. Although the role of miRNAs in regulating BM has been indicated, the underlying molecular mechanism is still poorly understood, especially in lung cancer.…”