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miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling

  • Authors:
    • Jianbo Dai
    • Yaqin Hao
    • Xun Chen
    • Qingsan Yu
    • Bin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400060, P.R. China, Department of Gastroenterology, The Fifth People's Hospital of Chongqing, Chongqing 400060, P.R. China, Department of Anesthesiology, Nan'an District People's Hospital of Chongqing, Chongqing 400060, P.R. China, Department of General Surgery, Nan'an District People's Hospital of Chongqing, Chongqing 400060, P.R. China
    Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 390
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    Published online on: July 24, 2023
       https://doi.org/10.3892/ol.2023.13976
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Abstract

The property of inherent stemness of tumor cells coupled with the development of chemoresistance results in a poor prognosis for patients with liver cancer. Therefore, the present study focused on microRNA (miR)‑122, a potential tumor suppressor, the expression of which has been previously shown to be significantly decreased and negatively associated with cancer cell stemness in liver cancer. The present study aimed to identify the molecular targets of miR‑122 whilst uncovering the mechanism underlying chemoresistance and stemness of HepG2 cells in liver cancer. Bioinformatics online tools, such as ENCORI, coupled with dual‑luciferase reporter assays in HepG2 cells, were used to identify and validate small ubiquitin‑like modifier (SUMO) specific peptidase 1 (SENP1) as a potential target of miR‑122 in liver cancer. The liver cancer stem cell population was determined using sphere formation assays and flow cytometry, whilst stem cell markers (Oct3/4, Nanog, B lymphoma Mo‑MLV insertion region 1 homolog and Notch1) were detected by reverse transcription‑quantitative PCR. Chemoresistance, cell proliferation and migratory ability of HepG2 cells were monitored using Cell Counting Kit‑8, colony formation and Transwell assays, respectively. The overexpression of miR‑122 by mimic transfection led to a significant decrease in the number spheres, downregulation of stem cell marker expression, the number of CD24+ cells, drug‑resistance protein levels (P‑glycoprotein and multidrug resistance protein), impaired chemoresistance, proliferation and migration of HepG2 cells. The transfection of SENP1 overexpression vector resulted in contrasting functions to miR‑122 mimics, by partially reversing the effects induced by miR‑122 mimic transfection in HepG2 cells. Wnt/β‑catenin signaling has been proven to be involved in cancer stemness and malignant behavior. Western blotting analysis in HepG2 cells showed that the expression levels of both Wnt1 and β‑catenin were significantly reduced after overexpressing miR‑122, but increased after overexpressing SENP1. Co‑transfection with the SENP1 overexpression vector reversed the suppression induced by the miR‑122 mimics on Wnt1 and β‑catenin expression. Co‑immunoprecipitation, SUMOylation and half‑life assays showed SENP1 interacted with β‑catenin and decreased the SUMOylation of β‑catenin, thereby enhancing its stability. Finally, tumor xenograft analyses revealed that HepG2 cells transfected with Agomir‑122 exerted significantly lower tumor initiation frequency and growth rate, and a superior response to DOX in vivo, compared with those transfected with Agomir NC. Taken together, data from the present study miR‑122/SENP1 axis can regulate β‑catenin stability through de‑SUMOylation, thereby promoting stemness and chemoresistance in liver cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Dai J, Hao Y, Chen X, Yu Q and Wang B: miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling. Oncol Lett 26: 390, 2023.
APA
Dai, J., Hao, Y., Chen, X., Yu, Q., & Wang, B. (2023). miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling. Oncology Letters, 26, 390. https://doi.org/10.3892/ol.2023.13976
MLA
Dai, J., Hao, Y., Chen, X., Yu, Q., Wang, B."miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling". Oncology Letters 26.3 (2023): 390.
Chicago
Dai, J., Hao, Y., Chen, X., Yu, Q., Wang, B."miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling". Oncology Letters 26, no. 3 (2023): 390. https://doi.org/10.3892/ol.2023.13976
Copy and paste a formatted citation
x
Spandidos Publications style
Dai J, Hao Y, Chen X, Yu Q and Wang B: miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling. Oncol Lett 26: 390, 2023.
APA
Dai, J., Hao, Y., Chen, X., Yu, Q., & Wang, B. (2023). miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling. Oncology Letters, 26, 390. https://doi.org/10.3892/ol.2023.13976
MLA
Dai, J., Hao, Y., Chen, X., Yu, Q., Wang, B."miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling". Oncology Letters 26.3 (2023): 390.
Chicago
Dai, J., Hao, Y., Chen, X., Yu, Q., Wang, B."miR‑122/SENP1 axis confers stemness and chemoresistance to liver cancer through Wnt/β‑catenin signaling". Oncology Letters 26, no. 3 (2023): 390. https://doi.org/10.3892/ol.2023.13976
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