MicroRNA-133a-3p Inhibits Lung Adenocarcinoma Development and Cisplatin Resistance through Targeting GINS4.

Abstract

GINS subunit complex 4 (GINS4) is fundamental to DNA replication and G1/S phase transition of the cell cycle in eukaryotes. Further, recent studies implied that GINS4 can mediate the progression of several tumors, but its mechanism in lung adenocarcinoma (LUAD) is not clarified. Therefore, the role of GINS4 in LUAD was explored. miR-133a-3p and GINS4 mRNA expression were tested through qRT-PCR. Protein levels of the two genes were assayed by Western blot. Their targeting relationship was predicted and verified by bioinformatics prediction and dual-luciferase analysis. The functions of miR-133a-3p and GINS4 in LUAD were evaluated by Transwell, wound healing, CCK-8, and flow cytometry assays. MTT assay and caspase-3 activity detection were utilized to measure the regulation of miR-133a-3p/GINS4 in the cisplatin sensitivity of LUAD cells. The results showed that GINS4 was highly expressed in LUAD cells (p < 0.05). miR-133a-3p, the upstream gene of GINS4 in LUAD, negatively mediated GINS4 expression. Moreover, overexpressing GINS4 enhanced the proliferative, migratory, and invasive abilities of LUAD cells and inhibited cell apoptosis and the sensitivity to cisplatin, while overexpressing miR-133a-3p caused the contrary results. However, the promoting effects of GINS4 overexpression on LUAD could be offset by miR-133a-3p overexpression. miR-133a-3p could regulate malignant behaviors and cisplatin sensitivity of LUAD cells through negatively regulating GINS4. In conclusion, our findings demonstrated that GINS4 was overexpressed in LUAD and promoted the malignant behavior of LUAD cells. Moreover, miR-133a-3p could negatively regulate GINS4, thereby suppressing the malignant progression and increasing the cisplatin sensitivity of LUAD.