Adenosine deaminase acting on RNA 1 p150 and p110 are involved in the proliferation,migration,and invasion of liver cancer cells

Gong Xue, Liu Jing, Jian Wenwen, Cui Yihong, Tu Zeng

PDF(9034 KB)
PDF(9034 KB)
Journal of Chongqing Medical University ›› 2024, Vol. 49 ›› Issue (07) : 820-829. DOI: 10.13406/j.cnki.cyxb.003544
Basic research

Adenosine deaminase acting on RNA 1 p150 and p110 are involved in the proliferation,migration,and invasion of liver cancer cells

Author information +
History +

Abstract

Objective To investigate the effect of adenosine deaminase acting on RNA 1(ADAR1) on the proliferation,migration,and invasion of liver hepatocellular carcinoma(LIHC) cells. Methods The gene expression profiling interactive analysis website GEPIA was used to obtain the expression level and prognostic value of ADAR1 in LIHC; proteins were extracted from human hepatocellular carcinoma specimens,and Western blot was used to measure the expression level of ADAR1. HepG2 and Huh7 cells were transfected with ADAR1 p150 and p110 overexpression plasmids or small interfering RNAs targeting both ADAR1 p150 and p110,and Western blot and qPCR were used to measure the expression of ADAR1 in cells after transfection. CCK-8 assay was used to observe the effect of ADAR1 on the proliferative ability of hepatocellular carcinoma cells,and scratch assay and Transwell assay were used to observe the effect of ADAR1 on the migration and invasion of LIHC cells. Finally,the DAVID online database was used to analyze the signaling pathways related to ADAR1,and Western blot was used to measure the expression of proteins associated with the signaling pathways. Results The protein expression level of ADAR1 in hepatocellular carcinoma tissue was significantly higher than that in paracancerous tissue,which was consistent with the prediction based on bioinformatics,and the high expression of ADAR1 was associated with the poor prognosis of hepatocellular carcinoma. CCK-8 assay showed that overexpression of ADAR1 promoted the proliferation ability of hepatocellular carcinoma cells(P<0.05),and knockdown of ADAR1 reduced the proliferation ability of hepatocellular carcinoma cells(P<0.05). Scratch assay and Transwell assay showed that overexpression of ADAR1 significantly promoted the migration and invasion of hepatocellular carcinoma cells(P<0.05),and knockdown of ADAR1 inhibited the migration and invasion abilities of hepatocellular carcinoma cells(P<0.05). The results of DAVID online analysis showed that ADAR1 was mainly enriched in the Wnt signaling pathway. Western blot showed that overexpression of ADAR1 inhibited the expression of GSK3β and the phosphorylation level of β-catenin,and knockdown of ADAR1 increased the expression of GSK3β and the phosphorylation level of β-catenin. Conclusion The results of this study show that there is a high expression level of ADAR1 in LIHC,which can activate the Wnt/β-catenin signaling pathway and thus promote the proliferation,migration,and invasion of hepatocellular carcinoma.

Key words

adenosine deaminase acting on RNA 1 / hepatocellular carcinoma / proliferation / migration and invasion / Wnt/β-catenin signaling pathway

Cite this article

Download Citations
Gong Xue , Liu Jing , Jian Wenwen , et al . Adenosine deaminase acting on RNA 1 p150 and p110 are involved in the proliferation,migration,and invasion of liver cancer cells. Journal of Chongqing Medical University. 2024, 49(07): 820-829 https://doi.org/10.13406/j.cnki.cyxb.003544

References

1
Anwanwan D Singh SK Singh S,et al. Challenges in liver cancer and possible treatment approaches[J]. Biochim Biophys Acta Rev Cancer20201873(1):188314.
2
Sperandio RC Pestana RC Miyamura BV,et al. Hepatocellular carcinoma immunotherapy[J]. Annu Rev Med202273:267-278.
3
Llovet JM De Baere T Kulik L,et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma[J]. Nat Rev Gastroenterol Hepatol202118(5):293-313.
4
Jiang C Sun XD Qiu W,et al. Conversion therapy in liver transplantation for hepatocellular carcinoma:what’s new in the era of molecular and immune therapy?[J]. Hepatobiliary Pancreat Dis Int202322(1):7-13.
5
Cannella R Lewis S da Fonseca L,et al. Immunotherapy-based treatments of hepatocellular carcinoma:AJR expert panel narrative review[J]. AJR Am J Roentgenol2022219(4):533-546.
6
Li H Wu ZY Chen JL,et al. External radiotherapy combined with sorafenib has better efficacy in unresectable hepatocellular carcinoma:a systematic review and meta-analysis[J]. Clin Exp Med202323(5):1537-1549.
7
Guo LL Hu CT Yao MW,et al. Mechanism of sorafenib resistance associated with ferroptosis in HCC[J]. Front Pharmacol202314:1207496.
8
Shen HQ An O Ren X,et al. ADARs act as potent regulators of circular transcriptome in cancer[J]. Nat Commun202213(1):1508.
9
Sun T Yu YP Wu XF,et al. Decoupling expression and editing preferences of ADAR1 p150 and p110 isoforms[J]. Proc Natl Acad Sci U S A2021118(12):e2021757118.
10
Quin J Sedmík J Vukić D,et al. ADAR RNA modifications,the epitranscriptome and innate immunity[J]. Trends Biochem Sci202146(9):758-771.
11
Fritzell K Xu LD Lagergren J,et al. ADARs and editing:the role of A-to-I RNA modification in cancer progression[J]. Semin Cell Dev Biol201879:123-130.
12
Shigeyasu K Okugawa Y Toden S,et al. AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer[J]. JCI Insight20183(12):e99976.
13
Dong XQ Chen G Cai ZX,et al. CDK13 RNA over-editing mediated by ADAR1 associates with poor prognosis of hepatocellular carcinoma patients[J]. Cell Physiol Biochem201847(6):2602-2612.
14
Luo J Gong LQ Yang YM,et al. Enhanced mitophagy driven by ADAR1-GLI1 editing supports the self-renewal of cancer stem cells in HCC[J]. Hepatology202479(1):61-78.
15
Chen LL Li Y Lin CH,et al. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma[J]. Nat Med201319(2):209-216.
16
Baker AR Miliotis C Ramírez-Moya J,et al. Transcriptome profiling of ADAR1 targets in triple-negative breast cancer cells reveals mechanisms for regulating growth and invasion[J]. Mol Cancer Res202220(6):960-971.
17
Chan TH Lin CH Qi LH,et al. A disrupted RNA editing balance mediated by ADARs(Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma[J]. Gut201463(5):832-843.
18
Yu JJ Zhang CJ Yu QS,et al. ADAR1 p110 enhances adhesion of tumor cells to extracellular matrix in hepatocellular carcinoma via up-regulating ITGA2 expression[J]. Med Sci Monit201925:1469-1479.
19
王 珉,徐子岩,于 超,等. 肝脏类器官在肝癌研究中的进展及其应用[J]. 中华肝脏病杂志202331(12):1332-1335.
Wang M Xu ZY Yu C,et al. Progress and application of liver organoids in liver cancer research[J]. Chin J Hepatol202331(12):1332-1335
20
Murai H Kodama T Maesaka K,et al. Multiomics identifies the link between intratumor steatosis and the exhausted tumor immune microenvironment in hepatocellular carcinoma[J]. Hepatology202377(1):77-91.
21
Hu SB Heraud-Farlow J Sun T,et al. ADAR1p150 prevents MDA5 and PKR activation via distinct mechanisms to avert fatal autoinflammation[J]. Mol Cell202383(21):3869-3884.e7.
22
Zhang B Li Y Zhang JY,et al. ADAR1 links R-loop homeostasis to ATR activation in replication stress response[J]. Nucleic Acids Res202351(21):11668-11687.
23
Yang WD Chen KH Yu Q,et al. ADAR1 is a prognostic biomarker and is correlated with immune infiltration in lung adenocarcinoma[J]. Cancer Med202312(13):14820-14832.
24
Cui HW Yi Q Tian M,et al. ADAR1 prevents R-loop accumulation-driven ATR pathway activation in ovarian cancer[J]. J Cancer202213(8):2397-2412.
25
Yang Q Xu P Liu QT,et al. Depleting DDX1 sensitizes non-small cell lung cancer cells to chemotherapy by attenuating cancer stem cell traits[J]. Life Sci2023323:121592.
26
Gajos-Michniewicz A Czyz M. WNT/β-catenin signaling in hepatocellular carcinoma:the aberrant activation,pathogenic roles,and therapeutic opportunities[J]. Genes Dis202411(2):727-746.
27
Chen X Zhang Y Zhang PP,et al. IGFBP2 drives epithelial-mesenchymal transition in hepatocellular carcinoma via activating the Wnt/β-catenin pathway[J]. Infect Agent Cancer202318(1):73.

Comments

PDF(9034 KB)

Accesses

Citation

Detail

Sections
Recommended

/