Li Shujie, Xie Yue, Zhou Wei, Zhou Qian, Tao Dan, Yang Haonan, Mao Kaijin, Li Shi, Lei Jinyan, Wu Yongzhong, Wang Ying
Radiation Oncology Center, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.
College of Bioengineering, Chongqing University, Chongqing, China.
Heliyon. 2023 Jun 3;9(6):e16868. doi: 10.1016/j.heliyon.2023.e16868. eCollection 2023 Jun.
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.
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.
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.
MALAT1 may function as a sponge for miR-140a-3p to enhance the PD-L1 expression and decrease the radiosensitivity of LUAD. Our results suggest that MALAT1 might be a promising therapeutic target for the radiotherapy sensitization of LUAD.
通过调节miR-140/PD-L1轴的表达，研究MALAT1对肺腺癌放射敏感性的调节作用。
分别在在线数据库UALCAN和dbDEMC中搜索肺腺癌（LUAD）患者的MALAT1和miR-140表达。然后在UALCAN和ONCOMIR数据库中分别分析它们与总生存率的关系。放疗后通过转染小干扰RNA或相应质粒对A549细胞进行功能分析。建立接受辐射的LUAD异种移植模型，以进一步观察MALAT1对LUAD放射敏感性的影响。进行荧光素酶测定和逆转录-聚合酶链反应，以评估miR-140与MALAT1或PD-L1之间的相互作用。
MALAT1在人LUAD肿瘤组织和细胞系中过表达，而miR-140受到抑制。MALAT1敲低或miR-140增加可抑制LUAD放疗后的细胞增殖并促进细胞凋亡。MALAT1敲低联合放疗也可抑制LUAD异种移植肿瘤的生长。miR-140可直接与MALAT1或PD-L1结合。此外，MALAT1敲低通过上调LUAD细胞中的miR-140来抑制PD-L1 mRNA和蛋白表达。
MALAT1可能作为miR-140a-3p的海绵，增强PD-L1表达并降低LUAD的放射敏感性。我们的结果表明，MALAT1可能是LUAD放疗增敏的一个有前景的治疗靶点。
