Liu Yongmei, Dong Yanhan, He Xinjia, Gong Anjing, Gao Jinning, Hao Xiaodan, Wang Shuai, Fan Yuqiao, Wang Zibo, Li Meng, Xu Wenhua
Department of Inspection, The Medical Faculty of Qingdao University, Qingdao, China.
Institute of Translational Medicine, Qingdao University, Qingdao, China.
Front Oncol. 2021 Jun 23;11:651915. doi: 10.3389/fonc.2021.651915. eCollection 2021.
Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses and , which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.
尽管近年来人们已经认识到PIWI相互作用RNA（piRNA）在癌症中的重要性，但关于piRNA在肺腺癌（LUAD）发生发展和进展中的作用及功能机制的研究仍然有限。在本研究中，我们鉴定出与正常组织相比，LUAD组织中有10种差异表达的piRNA，其中piR-hsa-211106在LUAD组织和细胞系中的表达水平下调。此外，通过功能获得和功能缺失分析检测了piR-hsa-211106对LUAD细胞恶性表型和化疗敏感性的影响，结果表明piR-hsa-211106抑制LUAD细胞增殖、肿瘤生长和迁移，但促进细胞凋亡。此外，我们的研究结果表明，piR-hsa-211106是一种潜在的治疗靶点，可与LUAD顺铂化疗药物协同发挥抗癌作用。进一步的机制研究表明，piR-hsa-211106可通过RNA下拉和RNA免疫沉淀实验与丙酮酸羧化酶（PC）结合，并抑制其mRNA和蛋白表达。我们的研究表明，piR-hsa-211106通过阻碍PC的表达和功能抑制LUAD进展，并增强化疗敏感性，提示piR-hsa-211106是LUAD的一个新的诊断和治疗靶点。
