4.7 Article

CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 235, Issue 10, Pages 6929-6941

Publisher

WILEY
DOI: 10.1002/jcp.29589

Keywords

cell cycle; circRNAs; hepatocellular carcinoma; HuR; p27

Funding

  1. Shandong Provincial Natural Science Foundation, China [ZR201702210502]
  2. National Key Research and Development Program of China [2016YFC0106004]
  3. National Nature Science Foundation of China [81772601, 81802414]
  4. Shandong Provincial Medicine and Health Science Technology Development Planning, China [2015WS0231]

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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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