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A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
Published on: October 24, 2015
Circ_0005075 promotes hepatocellular carcinoma progression by suppression of microRNA-335
Xiangyu Yang1, Hang Song2,3, Zhenguo Zi4
1Department of Interventional Radiology, Beijing Chao-yang Hospital Affiliated with Capital Medical University, Beijing, China.
Abstract:
Accumulating evidence suggests that noncoding RNAs play a vital role in cancer biology. Circular RNAs (circRNAs), a newly defined class of endogenously widespread noncoding RNAs, have been intensively reported to influence cell function and development, and even cancer prognosis by sponging microRNAs in various types of cancer. Nevertheless, the circRNAs research in hepatocellular carcinoma (HCC) still remains far insufficient. Herein, we investigated the role of a newly defined circRNAs, circ_0005075, in HCC development. We found circ_0005075 was upregulated in HCC tissues. HCC progression was suppressed by downregulation of circ_0005075 in vitro and in vivo, and the suppression was partially reversed by inhibition of microRNA-335 (miR-335) expression. Further, we found the expression of mitogen-activated protein kinase 1 (MAPK1) was substantially regulated by circ_0005075 and miR-335. Mechanically, it was demonstrated that circ_0005075 could directly bind to miR-335 and miR-335 could bind to MAPK1. Our data provide evidence that circ_0005705 promotes the HCC progression by sponging miR-335 and further regulating MAPK1 expression.
Insights
Circular RNAs (circRNAs) like circ_0005075 promote hepatocellular carcinoma (HCC) progression. Downregulating circ_0005075 inhibits HCC by sponging microRNA-335 (miR-335) and affecting MAPK1.
Area of Science:
- Molecular biology
- Cancer research
- RNA biology
Background:
- Noncoding RNAs, including circular RNAs (circRNAs), are crucial in cancer biology.
- circRNAs regulate gene expression and impact cancer prognosis by sponging microRNAs.
- Research on circRNAs in hepatocellular carcinoma (HCC) is limited.
Purpose of the Study:
- To investigate the role of circ_0005075 in HCC development.
- To elucidate the molecular mechanism of circ_0005075 in HCC progression.
Main Methods:
- Quantitative real-time PCR to measure circRNA and miRNA expression.
- In vitro and in vivo experiments to assess HCC progression.
- Western blotting to detect protein expression.
- RNA immunoprecipitation and dual-luciferase reporter assays to confirm interactions.
Main Results:
- circ_0005075 was significantly upregulated in HCC tissues compared to normal tissues.
- Downregulation of circ_0005075 suppressed HCC cell proliferation and migration in vitro and tumor growth in vivo.
- Inhibition of microRNA-335 (miR-335) partially reversed the suppressive effects of circ_0005075 downregulation.
- circ_0005075 directly bound to miR-335, and miR-335 targeted mitogen-activated protein kinase 1 (MAPK1).
- circ_0005075 promoted HCC progression by acting as a sponge for miR-335, thereby regulating MAPK1 expression.
Conclusions:
- circ_0005075 acts as an oncogenic circRNA in HCC progression.
- The circ_0005075/miR-335/MAPK1 axis represents a potential therapeutic target for HCC.
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