AKR1B10 inhibits the proliferation and metastasis of hepatocellular carcinoma cells by regulating the PI3K/AKT pathway

Tian,Ke; Deng,Ying; Li,Zhipeng; Zhou,Huaxin; Yao,Hui

doi:10.3892/ol.2023.14151

AKR1B10 inhibits the proliferation and metastasis of hepatocellular carcinoma cells by regulating the PI3K/AKT pathway

Authors:
- Ke Tian
- Ying Deng
- Zhipeng Li
- Huaxin Zhou
- Hui Yao
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Affiliations: Second Department of General Surgery, No. 2 People's Hospital of Lanzhou, Lanzhou, Gansu 730030, P.R. China, Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, Shandong 250000, P.R. China
Published online on: November 15, 2023 https://doi.org/10.3892/ol.2023.14151
Article Number: 18
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent and aggressive malignant neoplasms, and is associated with a poor prognosis. Therefore, there is a crucial need to develop novel cancer therapies and identify novel therapeutic targets. Aldo‑keto reductase family 1 member B10 (AKR1B10) is expressed in various types of cancer. However, the role of AKR1B10 in the pathological process of HCC and its underlying molecular mechanism is poorly understood. AKR1B10 expression was evaluated pan‑cancer and in HCC using the Genomic Data Commons‑The Cancer Genome Atlas (GDC‑TCGA) and International Cancer Genome Consortium (ICGC) databases. The relationship between elevated AKR1B10 expression and overall survival in HCC patients was analyzed using a Kaplan‑Meier plot. The effects of AKR1B10 on the proliferation, migration, and invasion of HCC cells were evaluated. The proliferation of HCC was measured using CCK‑8 and colony formation assays. Transwell and wound healing assays were used to assess the migration and invasion of HCC cells. Western blots were used to detect the expression of proliferative and epithelial‑mesenchymal transition (EMT) related proteins in HCC cells, including CCND1, E‑cadherin, N‑cadherin, vimentin, Twist1, PI3K/p‑PI3K, and AKT/p‑AKT. AKR1B10 expression was significantly upregulated pan‑cancer and in liver cancer. Upregulated AKR1B10 expression was associated with a worse overall survival. HCC cell proliferation, migration, and invasion were found to be influenced by AKR1B10 activity, as demonstrated using DepMap analysis. AKR1B10 knockdown in Huh7 cells reduced proliferation, migration, invasion, and EMT. Mechanistically, AKR1B10 increased the expression of proliferative and EMT‑related proteins CCND1, E‑cadherin, N‑cadherin, vimentin, and Twist1. PI3K and AKT phosphorylation levels decreased following AKR1B10 knockdown. In conclusion, AKR1B10 promoted the proliferation, migration, and invasion of HCC cells via the PI3K/AKT signaling pathway, a potential prognostic indicator.

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