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, CCK8 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, which was 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 overexpressed 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.


中文翻译：

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MicroRNA-133a-3p 通过靶向 GINS4 抑制肺腺癌发展和顺铂耐药

GINS 亚基复合物 4 (GINS4) 是真核生物中 DNA 复制和细胞周期 G1/S 相变的基础。此外，最近的研究表明 GINS4 可以介导几种肿瘤的进展，但其在肺腺癌 (LUAD) 中的机制尚不清楚。因此，探讨了 GINS4 在 LUAD 中的作用。通过 qRT-PCR 测试 MiR-133a-3p 和 GINS4 mRNA 表达。通过蛋白质印迹测定两个基因的蛋白质水平。它们的靶向关系通过生物信息学预测和双荧光素酶分析进行了预测和验证。通过 Transwell、伤口愈合、CCK8 和流式细胞术测定评估 LUAD 中 miR-133a-3p 和 GINS4 的功能。MTT法和caspase-3活性检测用于测量miR-133a-3p/GINS4对LUAD细胞顺铂敏感性的调节。结果显示，GINS4在LUAD细胞中高表达（P<0.05）。LUAD 中 GINS4 的上游基因 MiR-133a-3p 负介导 GINS4 表达。此外，过表达 GINS4 增强了 LUAD 细胞的增殖、迁移和侵袭能力，抑制了细胞凋亡和对顺铂的敏感性，而过表达的 miR-133a-3p 则导致相反的结果。然而，GINS4 过表达对 LUAD 的促进作用可以被 miR-133a-3p 过表达所抵消。MiR-133a-3p可通过负调控GINS4调控LUAD细胞的恶性行为和顺铂敏感性。总之，我们的研究结果表明 GINS4 在 LUAD 中过表达并促进了 LUAD 细胞的恶性行为。此外，miR-133a-3p 可以负调控 GINS4，