4.4 Article

Pseudogene Annexin A2 Pseudogene 1 Contributes to Hepatocellular Carcinoma Progression by Modulating Its Parental Gene ANXA2 via miRNA-376a-3p

Journal

DIGESTIVE DISEASES AND SCIENCES
Volume 66, Issue 11, Pages 3903-3915

Publisher

SPRINGER
DOI: 10.1007/s10620-020-06734-0

Keywords

Pseudogene; Hepatocellular carcinoma; Epithelial-mesenchymal transition; Metastasis

Funding

  1. Scientific Research Starting Program of Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan) [SRSP2019016]
  2. Medical Scientific Research Foundation of Guangdong Province of China [2017113015361]

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The pseudogene ANXA2P1 is significantly overexpressed in hepatocellular carcinoma (HCC) tissues and is associated with disease progression and poor prognosis in patients. ANXA2P1 acts as an oncogene by competing with miR-376a-3p, leading to the upregulation of the ANXA2 gene and promoting cell growth, migration, and invasion in HCC.
Background Pseudogenes are defined as key regulators in cancer initiation and progression. But their biological function and clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated. In the current study, we identified a novel pseudogene, Annexin A2 pseudogene 1 (ANXA2P1), in HCC and explored its underlining molecular mechanism. Methods and Results We analyzed the expression pattern of ANXA2P1 in a TCGA dataset and an HCC sample cohort and evaluated its clinical significance. The biological effects on HCC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were assessed by Cell Counting Kit-8 assay, Transwell assay and Western blot, respectively. The ANXA2P1/miR-376a-3p/ANXA2 axis was determined by bioinformatics analysis and dual-luciferase reporter assays. ANXA2P1 exerted as an oncogene that was significantly overexpressed in HCC tissues and was associated with disease progression and unfavorable prognosis of HCC patients. ANXA2P1 knockdown suppressed cell growth, cell migration and invasion and reversed EMT phenotype in HCC. Mechanistically, ANXA2P1 acts as a competing endogenous RNA for miR-376a-3p, thereby leading to the upregulation of its cognate gene ANXA2. Conclusions ANXA2P1/miR-376a-3p/ANXA2 axis plays an important role in the progression of HCC. Our findings may provide valuable therapeutic target for treating HCC.

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