Fourth Department of Hepatic Surgery, Second Military Medical University, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
Cancer Biother Radiopharm. 2020 Dec;35(10):731-740. doi: 10.1089/cbr.2019.2996. Epub 2020 May 12.
Hepatocellular carcinoma (HCC), the fourth leading cause of cancer-related deaths worldwide, has increased public concern. Data from previous work have validated that long noncoding RNAs are active participators in the malignant processes of a host of cancers. Small nucleolar RNA host gene 7 (SNHG7) has been revealed to act as a tumor promoter in several cancers and SNHG7 inhibition was revealed to suppress cell invasion in HCC. Nevertheless, the specific role of SNHG7 in HCC deserves deeper exploration. This work aimed to uncover the role and the regulatory mechanisms of SNHG7 in HCC. The expression of SNHG7 and cyclin mediator 1 (CNNM1) in HCC cells were analyzed by quantitative real-time polymerase chain reaction. The influences of SNHG7 on HCC occurrence were studied by cell counting kit-8 (CCK-8), colony formation, flow cytometry analysis, and Western blot assays. Luciferase reporter assay or RNA immunoprecipitation assay was conducted to confirm the relationship between miR-9-5p and SNHG7 (or CNNM1). SNHG7 was overexpressed in HCC tissues and cell lines. SNHG7 facilitated cell proliferation, while suppressed cell apoptosis in HCC. Moreover, miR-9-5p expression was negatively modulated by SNHG7 and therefore was downregulated in HCC cells. We also found that CNNM1 existed in miR-9-5p induced RNA-induced silencing complex and a series of assays verified that CNNM1 acted as the target gene of miR-9-5p. Consequently, the messenger RNA and protein level of CNNM1 were detected to be inversely regulated by miR-9-5p. Moreover, rescue assays demonstrated that CNNM1 overexpression could countervail the SNHG7 depletion-mediated cellular functions of HCC cells. SNHG7 sponges miR-9-5p to upregulate CNNM1 in promoting HCC progression.
肝细胞癌（HCC）是全球第四大癌症相关死亡原因，引起了公众的关注。以前的研究数据已经证实，长链非编码 RNA 是许多癌症恶性过程中的活跃参与者。小核仁 RNA 宿主基因 7（SNHG7）已被证实在几种癌症中作为肿瘤促进因子发挥作用，并且 SNHG7 抑制被证实抑制 HCC 中的细胞侵袭。然而，SNHG7 在 HCC 中的具体作用值得更深入的探索。本研究旨在揭示 SNHG7 在 HCC 中的作用和调节机制。通过实时定量聚合酶链反应分析 HCC 细胞中 SNHG7 和细胞周期蛋白介导物 1（CNNM1）的表达。通过细胞计数试剂盒-8（CCK-8）、集落形成、流式细胞术分析和 Western blot 分析研究 SNHG7 对 HCC 发生的影响。荧光素酶报告基因或 RNA 免疫沉淀分析用于证实 miR-9-5p 与 SNHG7（或 CNNM1）之间的关系。SNHG7 在 HCC 组织和细胞系中过表达。SNHG7 促进 HCC 细胞增殖，同时抑制细胞凋亡。此外，SNHG7 负调控 miR-9-5p 的表达，因此 HCC 细胞中 miR-9-5p 的表达下调。我们还发现 CNNM1 存在于 miR-9-5p 诱导的 RNA 诱导沉默复合物中，一系列实验验证了 CNNM1 是 miR-9-5p 的靶基因。因此，miR-9-5p 反式调节 CNNM1 的 mRNA 和蛋白水平。此外，挽救实验表明，CNNM1 的过表达可以抵消 SNHG7 耗竭介导的 HCC 细胞的细胞功能。SNHG7 通过海绵 miR-9-5p 上调 CNNM1 促进 HCC 进展。
