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

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.

AKR1B10 expression characteristics in hepatocellular carcinoma and its correlation with clinicopathological features and immune microenvironment

“…Multiple studies have confirmed that in patients infected with hepatitis C virus (HCV) 34 and hepatitis B virus (HBV) 35 , high expression of AKR1B10 is an independent prognostic factor predicting HCC development, and AKR1B10 may even be a molecular marker reflecting the progression from steatohepatitis to HCC 36 . Recent studies have revealed that AKR1B10 promotes the proliferation, migration, and invasion of HCC cells through the PI3K/AKT signaling pathway 37 . These findings are consistent with our gene enrichment analysis results, indicating that AKR1B10 may affect the biological characteristics of HCC by regulating inflammation-related signaling pathways, thereby affecting tumor development and patient prognosis.…”

Aldo-keto reductases: Role in cancer development and theranostics

“…Evaluation of the Genomic Data Commons-The Cancer Genome Atlas (GDC-TCGA) and the International Cancer Genome Consortium (ICGC) databases revealed a significant elevation in AKR1B10 expression in HCC. The increase in AKR1B10 was associated with cell proliferation, migration, invasion, and EMT that contribute to metastasis as evidenced by increased expression of CCND1, E-cadherin, N-cadherin, vimentin, and Twist1 via activation of the PI3K/AKT signaling pathway [ 131 ]. Cheng et al [ 132 ] reported elevated expression of AKR1B1 in gastric cancer cells associated with enhanced cell proliferation, migration, and invasion.…”