Department of Oncology, the First Hospital of Qinhuangdao, Qinhuangdao, China.
Department of Oncology, Wuqing People's Hospital, Tianjin, China.
Am J Physiol Gastrointest Liver Physiol. 2021 May 1;320(5):G816-G828. doi: 10.1152/ajpgi.00209.2020. Epub 2020 Nov 25.
Upregulating the expression of long noncoding RNA LINC00982 controlled cell proliferation in gastric cancer, but the regulatory molecular mechanisms are yet to be expounded. We here aimed to elaborate how LINC00982 regulated the malignancy of gastric cancer cells. RT-qPCR and Western blot analysis were used to detect the expression of LINC00982 and cathepsin F (CTSF) in gastric cancer tissues and cells. Modulatory effect of LINC00982 on gastric cancer cells was assessed by CCK-8, colony formation, Transwell migration, and invasion assays. The relationship between LINC00982, YRPW motif 1 (HEY1), and CTSF was examined by RNA-binding protein immunoprecipitation, luciferase assay, and chromatin immunoprecipitation, and their interaction in the regulation of gastric cancer cellular functions was analyzed by performing gain-of-function and rescue assays. The nude mouse model of tumor formation was developed to examine the effects of LINC00982 on tumorigenesis. LINC00982 was lowly expressed in gastric cancer tissues, whereas its overexpression impaired the proliferative, migratory, and invasive properties of gastric cancer cells. Furthermore, LINC00982 could bind to transcription factor HEY1 and inhibited its expression. Through blocking the binding of HEY1 to CTSF promoter, LINC00982 promoted the expression of CTSF. Overexpression of HEY1 or inhibition of CTSF could reverse the antitumor effects of LINC00982 on gastric cancer, which were further demonstrated in vivo. All these taken together, LINC00982 acted as a tumor suppressor in gastric cancer, which is therefore suggested to be a potential antitumor target for gastric cancer. We identified LINC00982 as a promising antitumor target for the treatment of patients with gastric cancer. We also determined a regulatory network involved in the pathophysiology of gastric cancer wherein LINC00982 could bind to HEY1 to impair its binding to cathepsin F (CTSF) promoter and hence promote CTSF expression, which aids in better understanding of molecular mechanisms related to gastric tumorigenesis.
上调长链非编码 RNA LINC00982 的表达可控制胃癌细胞增殖，但调控的分子机制尚待阐明。本研究旨在阐述 LINC00982 如何调控胃癌细胞的恶性表型。采用 RT-qPCR 和 Western blot 分析检测胃癌组织和细胞中 LINC00982 和组织蛋白酶 F（CTSF）的表达。通过 CCK-8、集落形成、Transwell 迁移和侵袭实验评估 LINC00982 对胃癌细胞的调控作用。采用 RNA 结合蛋白免疫沉淀、荧光素酶报告基因和染色质免疫沉淀实验检测 LINC00982、YRPW 基序 1（HEY1）和 CTSF 之间的关系，并通过进行功能获得和挽救实验分析它们在调控胃癌细胞功能中的相互作用。建立裸鼠肿瘤形成模型，检测 LINC00982 对肿瘤发生的影响。LINC00982 在胃癌组织中低表达，而过表达则削弱了胃癌细胞的增殖、迁移和侵袭能力。此外，LINC00982 可与转录因子 HEY1 结合并抑制其表达。通过阻断 HEY1 与 CTSF 启动子的结合，LINC00982 促进 CTSF 的表达。过表达 HEY1 或抑制 CTSF 可逆转 LINC00982 对胃癌的抗肿瘤作用，这在体内得到进一步证实。综上所述，LINC00982 在胃癌中发挥抑癌作用，因此提示其可能成为胃癌的潜在抗肿瘤靶点。我们确定 LINC00982 是治疗胃癌患者的有前途的抗肿瘤靶点。我们还确定了一个涉及胃癌病理生理学的调控网络，其中 LINC00982 可与 HEY1 结合，从而削弱其与组织蛋白酶 F（CTSF）启动子的结合，并促进 CTSF 的表达，这有助于更好地理解与胃肿瘤发生相关的分子机制。
