Association of long noncoding RNA MALAT1 with the radiosensitivity of lung adenocarcinoma cells via the miR-140/PD-L1 axis

作者：Shujie Li, Yue Xie, Wei Zhou, Qian Zhou, Dan Tao, Haonan Yang, Kaijin Mao, Shi Li, Jinyan Lei, Yongzhong Wu, Ying Wang · 发表于：Heliyon · 年份：2023 · DOI：10.1016/j.heliyon.2023.e16868 · 被引用次数：10 · 研究领域：Cancer-related molecular mechanisms research、MicroRNA in disease regulation、Circular RNAs in diseases

Objective: To investigate the effect of MALAT1 on the modulating the radiosensitivity of lung adenocarcinoma, through regulation of the expression of the miR-140/PD-L1 axis. Methods: The online databases UALCAN and dbDEMC were searched for the MALAT1 and miR-140 expressions in patients with lung adenocarcinoma (LUAD), respectively. Then analyze their relationship with overall survival rates separately in the UALCAN and ONCOMIR databases. A functional analysis was performed for A549 cells by transfecting small-interfering RNAs or corresponding plasmids after radiotherapy. Xenograft models of LUAD exposed to radiation were established to further observe the effects of MALAT1 on the radiosensitivity of LUAD. The luciferase assay and reverse transcription-polymerase chain reaction were performed to assess the interaction between miR-140 and MALAT1 or PD-L1. Results: MALAT1 were overexpressed in human LUAD tumor tissues and cell lines, while miR-140 were inhibited. MALAT1 knockdown or miR-140 increase suppressed cell proliferation and promoted cell apoptosis in LUAD after irradiation. LUAD xenograft tumor growth was also inhibited by MALAT1 knockdown combined with irradiation. miR-140 could directly bind with MALAT1 or PD-L1. Furthermore, MALAT1 knockdown inhibited PD-L1 mRNA and protein expressions by upregulating miR-140 in LUAD cells. Conclusion: MALAT1 may function as a sponge for miR-140a-3p to enhance the PD-L1 expression and decrease the radiosensitivity of LUAD. Our result...