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CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR
Bingqi Liu1, Guangsheng Yang1, Xin Wang2
1Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
Insights
Circular RNAs (circRNAs) like circBACH1 are upregulated in hepatocellular carcinoma (HCC), promoting tumor growth. This study reveals circBACH1 acts as an oncogene by regulating the HuR/p27 axis in HCC.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers.
- The specific functions of most circRNAs in hepatocellular carcinoma (HCC) remain largely uncharacterized.
- Understanding novel molecular mechanisms in HCC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role and mechanism of circBACH1 in hepatocellular carcinoma (HCC) development.
- To elucidate the molecular pathway involving circBACH1, HuR, and p27 in HCC progression.
- To determine the potential of circBACH1 as a prognostic biomarker and therapeutic target in HCC.
Main Methods:
- Quantification of circBACH1 expression in HCC tissues and correlation with clinical prognosis.
- In vitro and in vivo experiments to assess the effect of circBACH1 on HCC cell proliferation and cell cycle.
- RNA immunoprecipitation, pull-down assays, electrophoretic mobility shift assays, fluorescence in situ hybridization, and immunofluorescence to investigate molecular interactions and localization.
Main Results:
- circBACH1 was significantly upregulated in HCC tissues and associated with poor patient prognosis.
- circBACH1 overexpression promoted HCC cell cycle progression and tumor growth.
- circBACH1 directly bound to HuR, facilitating its translocation to the cytoplasm and inhibiting p27 translation, thereby promoting HCC proliferation.
Conclusions:
- circ BACH1 functions as an oncogene in hepatocellular carcinoma.
- The circBACH1/HuR/p27 signaling axis plays a critical role in HCC development and progression.
- circBACH1 represents a potential therapeutic target and prognostic marker for HCC.
Abstract:
In recent years, an increasing number of circular RNAs (circRNAs) have been discovered in hepatocellular carcinoma (HCC). However, the functions of most circRNAs require further investigation. Here, we found that circBACH1 was significantly upregulated in HCC tissues and that high circBACH1 levels were closely associated with poor prognosis. In addition, circBACH1 could promote HCC growth by accelerating cell cycle progression in vitro and in vivo. We next investigated the cellular and molecular mechanisms and discovered that circBACH1 inhibited p27 translation, which influenced cell cycle progression. Moreover, we revealed that circBACH1 could combine directly with HuR using RNA immunoprecipitation assays, pull-down assays, and electrophoretic mobility shift assays. The combination of these molecules facilitated HuR translocation from the nucleus to the cytoplasm according to the fluorescence in situ hybridization and immunofluorescence results. Finally, silencing HuR abrogated circBACH1's inhibition of p27 translation and abolished the circBACH1-induced effect on HCC proliferation. In sum, circBACH1 plays a significant role as an oncogene through the circBACH1/HuR/p27 axis in HCC development.
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