Tian Qing, Yan Xiaodong, Yang Long, Liu Zirong, Yuan Zheyue, Zhang Yamin
Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, P.R China.
Tianjin Key Laboratory for Transplantation, First Central Clinic of Tianjin Medical University, Tianjin 300192, P.R China.
Oncol Lett. 2021 Nov;22(5):796. doi: 10.3892/ol.2021.13057. Epub 2021 Sep 17.
Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide with high morbidity and high mortality rates. Previous studies have demonstrated that cytoskeleton regulator RNA (CYTOR) plays critical roles in the tumorigenesis of various types of cancer. The present study aimed to investigate the clinical significance, biological function and molecular mechanism of CYTOR in the progression of HCC. The expression level of CYTOR was determined by reverse transcription quantitative PCR in HCC tissues and cell lines. The biological function of CYTOR was investigated using CCK-8 assay, EdU immunofluorescence, western blotting and TUNEL assay . A xenograft tumor model and immunohistochemistry were used to validate the role of CYTOR . The downstream targets of CYTOR and micro-RNA (miR)-125b were confirmed by RNA immunoprecipitation assay and luciferase reporter assays. The results demonstrated that CYTOR was significantly increased in HCC tissues compared with non-tumor tissues and that CYTOR expression was associated with the poor prognosis of patients with HCC. Furthermore, CYTOR silencing could inhibit the proliferation and promote the apoptosis of HCC cells. CYTOR overexpression had the opposite effects. The results from xenograft demonstrated that CYTOR knockdown suppressed tumor growth. In addition, CYTOR could directly interact with and negatively regulate miR-125b. Furthermore, semaphorin 4C (SEMA4C) was the target of miR-125b and CYTOR regulated SEMA4C expression by modulating miR-125b. Taken together, the findings from the present study demonstrated that CYTOR could promote cell proliferation and tumor growth by sponging miR-125b and upregulating SEMA4C, which suggested that CYTOR may act as a potential therapeutic target in HCC.
肝细胞癌（HCC）是全球常见的恶性肿瘤，发病率和死亡率都很高。先前的研究表明，细胞骨架调节RNA（CYTOR）在各类癌症的肿瘤发生过程中发挥着关键作用。本研究旨在探讨CYTOR在HCC进展中的临床意义、生物学功能及分子机制。通过逆转录定量PCR检测HCC组织和细胞系中CYTOR的表达水平。采用CCK-8检测、EdU免疫荧光、蛋白质免疫印迹和TUNEL检测等方法研究CYTOR的生物学功能。利用异种移植肿瘤模型和免疫组织化学验证CYTOR的作用。通过RNA免疫沉淀检测和荧光素酶报告基因检测确定CYTOR和微小RNA（miR）-125b的下游靶点。结果表明，与非肿瘤组织相比，HCC组织中CYTOR显著升高，且CYTOR表达与HCC患者的不良预后相关。此外，CYTOR沉默可抑制HCC细胞增殖并促进其凋亡。CYTOR过表达则产生相反的效果。异种移植实验结果表明，CYTOR敲低可抑制肿瘤生长。此外，CYTOR可直接与miR-125b相互作用并对其进行负调控。此外，信号素4C（SEMA4C）是miR-125b的靶点，CYTOR通过调节miR-125b来调控SEMA4C的表达。综上所述，本研究结果表明，CYTOR可通过吸附miR-125b并上调SEMA4C来促进细胞增殖和肿瘤生长，这表明CYTOR可能是HCC潜在的治疗靶点。
