Effects of MicroRNA‐195‐5p on Biological Behaviors and Radiosensitivity of Lung Adenocarcinoma Cells via Targeting HOXA10

Abstract

Objective. To explore the effects of miR-195-5p and its target gene HOXA10 on the biological behaviors and radiosensitivity of lung adenocarcinoma (LUAD) cells. Methods. The effects of miR-195-5p on LUAD cell proliferation, migration, invasion, cycle arrest, apoptosis, and radiosensitivity were investigated by in vitro experiments. The bioinformatics analysis was used to assess its clinical value and predict target genes. Double-luciferase experiments were used to verify whether the miR-195-5p directly targeted HOXA10. A xenograft tumor-bearing mouse model was used to examine its effects on the radiosensitivity of LUAD in vivo. Results. Both gain- and loss-of-function assays demonstrated that miR-195-5p inhibited LUAD cell proliferation, invasion, and migration, induced G1 phase arrest and apoptosis, and enhanced radiosensitivity. Double-luciferase experiments confirmed that miR-195-5p directly targeted HOXA10. Downregulation of HOXA10 also inhibited LUAD cell proliferation, migration, and invasion, induced G1 phase arrest and apoptosis, and enhanced radiosensitivity. The protein levels of β-catenin, c-myc, and Wnt1 were decreased by miR-195-5p and increased by its inhibitor. Moreover, the effects of the miR-195-5p inhibitor could be eliminated by HOXA10-siRNA. Furthermore, miR-195-5p improved radiosensitivity of LUAD cells in vivo. Conclusion. miR-195-5p has excellent antitumor effects via inhibiting cancer cell growth, invasion, and migration, arresting the cell cycle, promoting apoptosis, and sensitizing LUAD cells to X-ray irradiation by targeting HOXA10. Thus, miR-195-5p may serve as a potential candidate for the treatment of LUAD.

Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling

“…As demonstrated by recent studies, strong invasiveness and metastasis are distinctive features of LUAD [ 21 ]. To analyze the impacts of ORC1 on the migrative and invasive capacities of LUAD cells.…”

MicroRNA-195-5p targets neurofibromin 2 to mediate hyperoxia-induced alveolar dysplasia

“…Silencing miR-195-5p inhibits the TGF-β1-Smad-Snail pathway by targeting Smad7, thereby inhibiting endothelial mesenchymal transition and alleviating myocardial fibrosis in diabetic cardiomyopathy (49). Additionally, miR-195-5p inhibits the proliferation of LUAD cells by targeting HOXA10 to inhibit the Wnt/β-catenin signaling pathway (50). Wnt3A, fibroblast growth factor 2 (FGF2), and BMPR1A are direct targets of miR-195-5p.…”

“…miR-195-5p directly targets HOXA10 to inhibit the growth, invasion, and migration of lung cancer cells; block cell cycle; and promote apoptosis (15). For instance, hsa-miR-195-5p may be used as a diagnostic biomarker for lung cancer (16).…”

MiRNA-Based Therapies for Lung Cancer: Opportunities and Challenges?

“…For example, miR-519a arrests the cell cycle in G0/G1 by inhibiting the expression of the EphrinA2 receptor (EphA2) [ 79 ]. MiR-195-5p targets HOXA10, leading to G1 phase block and apoptosis [ 80 ]. MiR-30a induces G2/M checkpoint block by targeting activating transcription factor 1 (ATF1) [ 81 ].…”