Chen Wei, Huang Li, Liang Junhua, Ye Yingjian, Yu Sihao, Zhang Yijing
Department of Gastroenterology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
Department of Neurology, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
IUBMB Life. 2021 Feb;73(2):349-361. doi: 10.1002/iub.2431. Epub 2020 Dec 28.
Extensive studies have explored the involvements of long noncoding RNAs (lncRNAs) in liver cancer. Limitedly, the concrete function of lncRNA small nucleolar RNA host gene 15 (SNHG15) is still elusive. Therefore, the work was initiated to unearth SNHG15-oriented mechanism in liver cancer. Liver cancer tissues were resected. The connection between SNHG15 expression with prognosis and clinicopathological traits of liver cancer patients was evaluated. Liver cancer cells SMMC-7721 were transfected with restored microRNA (miR)-18b-5p or depleted SNHG15 to discover their effects on the proliferation, migration, invasion, cycle arrest, and apoptosis of SMMC-7721 cells. The transfected SMMC-7721 cells were injected into nude mice for further investigation. SNHG15, miR-18b-5p, and LIM-only 4 (LMO4) expressions in tissues and cells were tested. The regulatory connections among SNHG15, miR-18b-5p, and LMO4 were detected. SNHG15 and LMO4 were overexpressed while miR-18b-5p was downregulated in liver cancer tissues and cells. Up-regulated SNHG15 was connected with inferior prognosis and aggressive behaviors of liver cancer patients. SNHG15 knockdown or miR-18b-5p restoration depressed SMMC-7721 cell growth in vivo and in vitro. SNHG15 bound to miR-18b-5p and miR-18b-5p targeted LMO4. The work has illuminated that silencing SNHG15 represses liver cancer progression by modulating miR-18b-5p and LMO4, indicating the therapeutic potency of SNHG15/miR-18b-5p/LMO4 axis in liver cancer.
广泛的研究已经探索了长链非编码RNA（lncRNA）在肝癌中的作用。然而，lncRNA小核仁RNA宿主基因15（SNHG15）的具体功能仍不清楚。因此，本研究旨在揭示肝癌中SNHG15相关的机制。收集肝癌组织，评估SNHG15表达与肝癌患者预后及临床病理特征之间的关系。对肝癌细胞SMMC-7721进行miR-18b-5p过表达或SNHG15敲低转染，以研究其对SMMC-7721细胞增殖、迁移、侵袭、细胞周期阻滞和凋亡的影响。将转染后的SMMC-7721细胞注射到裸鼠体内进行进一步研究。检测组织和细胞中SNHG15、miR-18b-5p和仅含LIM结构域4（LMO4）的表达。检测SNHG15、miR-18b-5p和LMO4之间的调控关系。肝癌组织和细胞中SNHG15和LMO4表达上调，而miR-18b-5p表达下调。SNHG15上调与肝癌患者预后不良和侵袭性生物学行为相关。敲低SNHG15或过表达miR-18b-5p可抑制SMMC-7721细胞在体内外的生长。SNHG15与miR-18b-5p结合，miR-18b-5p靶向LMO4。本研究表明，沉默SNHG15通过调节miR-18b-5p和LMO4抑制肝癌进展，提示SNHG15/miR-18b-5p/LMO4轴在肝癌治疗中的潜力。
