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

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Abstract

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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Availability of data and materials

All data that support the findings of this study are available from the corresponding authors upon reasonable request.

Abbreviations

HCC:

Hepatocellular carcinoma

ANXA2P1:

Annexin A2 pseudogene 1

EMT:

Epithelial-mesenchymal transition

RPMI:

Roswell Park Memorial Institute

DMEM:

Dulbecco’s Modified Eagle Medium

CCK-8:

Cell Counting Kit 8

lncRNAs:

Long non-coding RNAs

PTENP1:

PTEN tumor suppressor

qRT-PCR:

Quantitative real-time polymerase chain reaction

EdU:

5-Ethynyl-2′-deoxyuridine

TCGA:

The Cancer Genome Atlas

BP:

Biological process

CC:

Cellular component

MF:

Molecular function

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Acknowledgment

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

Funding

This study was funded by the Scientific Research Starting Program of Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan) (SRSP2019016) and Medical Scientific Research Foundation of Guangdong Province of China (2017113015361).

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Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde, Foshan), No. 1 Jiazi Road, Lunjiao, Shunde District, Foshan, 528308, Guangdong Province, China

    Huohui Ou, Qingbo Liu, Jie Lin, Wei He, Weijie Zhang, Jing Ma & Weidong Wang

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  1. Huohui Ou
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  2. Qingbo Liu
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  3. Jie Lin
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  4. Wei He
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Contributions

Weidong Wang designed and supervised the study. Huohui Ou and Qingbo Liu performed the experiments and acquired result data. Jie Lin and Wei He collected the patient samples and information. Weijie Zhang and Jing Ma helped to review the statistical analysis. Huohui Ou drafted the manuscript. Weidong Wang and Qingbo Liu critically revised the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Weidong Wang.

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This animal research was approved by the Ethical Committee of Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde).

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Figure S1.

Expression of ANXA2P1 in TCGA samples cohort. (JPEG 68 kb)

Figure S2.

The positive correlation between ANXA2P1 and ANXA2 in TCGA samples cohort. (JPEG 94 kb)

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Ou, H., Liu, Q., Lin, J. et al. Pseudogene Annexin A2 Pseudogene 1 Contributes to Hepatocellular Carcinoma Progression by Modulating Its Parental Gene ANXA2 via miRNA-376a-3p. Dig Dis Sci 66, 3903–3915 (2021). https://doi.org/10.1007/s10620-020-06734-0

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