LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis
LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis
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DOI：
10.3389/fbioe.2020.00054
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发表时间：
2020-02-18
影响因子：
5.7
通讯作者：
Wei, Feng
中科院分区：
文献类型：
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作者：
Jin, Jinglan;Xu, Hongqin;Wei, Feng
肝细胞癌（Hepatocellular carcinoma，HCC）是肝癌的重要类型之一。LncRNA是一种重要的调节因子，在肿瘤发生和转移过程中调节许多生物学过程，如肿瘤细胞。LINC 00346与多种类型的肝癌相关，但其在HCC中的作用和调控机制尚不清楚。本研究通过生物信息学分析发现LINC 00356-miR-199 a-3 p-CDK 1/CCNB 1轴。通过qRT-PCR和WB检测HCC和正常肝细胞中LINC 00356、miR-199 a-3 p、CDK 1和CCNB 1的表达。结果显示，LINC 00356、CDK 1和CCNB 1在HCC中高表达，而miR-199 a-3 p低表达。双荧光素酶报告基因测定、RIP和RNA下拉测定证明了LINC 00346-miR-199 a-3 p-CDK 1/CCNB 1的靶向结合关系。过表达LINC 00460和沉默miR-199 a-3 p可促进HCC细胞侵袭，抑制HCC细胞凋亡，使细胞周期阻滞于S期，而沉默LINC 00346、CDK 1和CCNB 1则相反。LINC 00346通过竞争性吸附miR-199 a-3 p促进CDK 1/CCNB 1表达间接影响肝癌。此外，该研究还证明，LINC 00346的过表达通过促进CDK 1/CCNB 1的表达间接抑制p53和p21蛋白的表达，从而阻断p53信号通路。以上结果证明LINC 00346可以通过竞争性吸附miR-199 a-3 p来调控CDK 1/CCNB 1的表达，从而影响p53信号通路，最终调控肝癌细胞的凋亡、侵袭和细胞周期。因此，LINC 00346可以作为一种肿瘤促进剂和潜在的治疗靶点，用于HCC的转移和预后。
Hepatocellular carcinoma (HCC) is one of the important types of liver cancer. LncRNA is an important regulatory factor that regulates many biological processes such as tumor cells during tumorigenesis and metastasis. LINC00346 has been associated with various types of liver cancer, but its role and regulatory mechanism in HCC remain unclear. In our study, we found the LINC00356-miR-199a-3p-CDK1/CCNB1 axis through bioinformatics analysis. The expressions of LINC00356, miR-199a-3p, CDK1, and CCNB1 in HCC and normal hepatocytes were determined by qRT-PCR and WB. The results showed that LINC00356, CDK1 and CCNB1 were highly expressed in HCC, while miR-199a-3p was lowly expressed. Dual luciferase reporter gene assay, RIP and RNA-pull down assays demonstrated the targeted binding relationship of LINC00346-miR-199a-3p-CDK1/CCNB1. Overexpressing LINC00460 and silencing miR-199a-3p promoted cell invasion, inhibited apoptosis of HCC, and arrested the cell cycle in S phase while opposite results were obtained when silencing LINC00346, CDK1, and CCNB1. LINC00346 indirectly affects liver cancer by promoting the expression of CDK1/CCNB1 through competitive adsorption of miR-199a-3p. In addition, the study also demonstrated that overexpression of LINC00346 indirectly inhibited the expression of p53 and p21 proteins by promoting CDK1/CCNB1 expressions, thereby blocking the p53 signaling pathway. These results proved that LINC00346 could regulate the expression of CDK1/CCNB1 through the competitive adsorption of miR-199a-3p, thereby affecting the p53 signaling pathway and finally regulating the apoptosis, invasion and cell cycle of HCC cells. In conclusion, LINC00346 can be used as a tumor promoter and potential therapeutic target for HCC metastasis and prognosis.