miR‑145 inhibits human non‑small-cell lung cancer growth by dual-targeting RIOK2 and NOB1

miR-145 通过双重靶向 RIOK2 和 NOB1 抑制人类非小细胞肺癌生长

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作者:Kun Liu, Honglin Chen, Qingsheng You, Qing Ye, Fei Wang, Shuo Wang, Shuanglong Zhang, Kangjun Yu, Weinan Li, Mingming Gu

Abstract

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide. Right open reading frame kinase 2 (RIOK2) and nin one binding protein (NOB1) are important accessory factors in ribosome assembly. In our previous study, RIOK2 and NOB1 were revealed to be highly expressed in NSCLC, and were associated with the clinicopathological characteristics of patients with NSCLC, i.e. TNM clinical stage, lymph node metastasis and differentiation. In addition, RIOK2 expression was correlated with NOB1. To further explore the mechanism and the RIOK2 and NOB1 signaling pathway, microRNA (miR) regulation was analyzed. The tumor suppressor miR‑145 has been reported to be lowly expressed in numerous types of human cancer; in the present study, the expression levels of miR‑145 were decreased in patients with NSCLC. Furthermore, RIOK2 and NOB1 were predicted to be the direct targets of miR‑145 using bioinformatics software; this was further validated using a dual luciferase reporter assay. In addition, the protein expression levels of RIOK2 and NOB1 were inhibited in response to miR‑145 overexpression, thus resulting in the suppression of cell viability, migration and invasion. These results suggested that RIOK2 and NOB1 may be potential targets in the treatment of NSCLC, and miR‑145 may be considered a therapeutic inhibitor of both genes.

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