miR‑296‑3p targets APEX1 to suppress cell migration and invasion of non‑small‑cell lung cancer

Abstract

Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-associated mortality worldwide. MicroRNAs (miRs) are a class of small non-coding RNAs that are commonly dysregulated in human cancer. The aim of the current study was to evaluate the effect of miR-296-3p on the cell migration and invasion of NSCLC. Pairs of tumor tissues and para-cancerous tissues (n=50) were collected from patients with NSCLC, and the expression of miR-296-3p was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, tumor cell viability, migration and invasion were examined in vitro using Cell Counting Kit-8, wound healing and Matrigel assays, respectively. Furthermore, potential targets of miR-296-3p were screened for using TargetScan and validated using a dual-luciferase reporter assay. The expression levels of phosphoinositide-3-kinase (PI3K), AKT serine/threonine kinase (AKT), mammalian target of rapamycin (mTOR), matrix metallopeptidase 2 (MMP2) and SRY-box 4 (SOX4) were detected by RT-qPCR and western blot analysis. The data indicated that miR-296-3p was downregulated in tumor tissues compared with adjacent normal tissues. Overexpression of miR-296-3p inhibited NSCLC cell viability, migration and invasion in vitro. Furthermore, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) was identified as a direct target of miR-296-3p. APEX1 expression was upregulated in tumor tissues compared with para-cancerous tissues, and the mRNA and protein expression levels of APEX1 were decreased following transfection of NSCLC cells with miR-296-3p mimics compared with control cells. Additional investigations revealed that miR-296-3p was involved in regulating the PI3K/AKT/mTOR signaling pathway, and miR-296-3p mimics decreased the mRNA and protein expression levels of MMP2 and SOX4. In summary, the findings demonstrated that miR-296-3p may function as a tumor suppressor, and inhibits the migration and invasion of NSCLC cells by targeting APEX1. miR-296-3p is therefore a potential therapeutic molecular modulator of NSCLC.

Non-Coding RNAs in Lung Tumor Initiation and Progression

“…The role of various lncRNA in regard to lung tumor development and progression is still subject for further study. As for the role of miRNA, it was found that the overexpression of miR-296-3p reduced the level of phosphorylation in this pathway without reducing mRNA expression by targeting apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1), therefore possibly inhibiting the pathway's progression particularly in NSCLC [241]. Additionally, miR-296-3p has been reported to have lower levels of expression in comparison to normal lung epithelial cells, and it played a role in inhibiting NSCLC cell proliferation as well as cisplatin sensitivity by targeting C-X3-C motif chemokine receptor 1(CX3CR1) which is upstream of PI3K signaling [242].…”

HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

“…Moreover, HDAC3 overexpression is documented to promote CRC proliferation and invasion [ 8 ]. MicroRNAs-296-3p (miR-296-3p) serves as a suppressor in malignancies including non-small-cell lung cancer, choroidal melanoma and glioblastoma [ 9 – 11 ]. Widely, it is implied that miR-296 is a suppressor of CRC cell progression and tumor growth [ 12 ].…”

Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression

“…The complex role of miR-296-3p as an oncogene or tumor suppressor has been described in several cancer types but has rarely been described in PTC [24][25][26][27] . Here, we found that the expression of miR-296-3p was significantly decreased in PTC tissues compared with adjacent tissues using qRT-PCR ( Fig.…”