Loss of AKR1B10 promotes colorectal cancer cells proliferation and migration via regulating FGF1-dependent pathway

Abstract

Colorectal cancer (CRC) is a common malignancy worldwide with poor prognosis and survival rates. The aldo-keto reductase family 1 member B10 (AKR1B10) plays an important role in metabolism, cell proliferation and mobility, and is downregulated in CRC. We hypothesized that AKR1B10 would promote CRC genesis via a noncanonical oncogenic pathway and is a novel therapeutic target. In this study, AKR1B10 expression levels in 135 pairs of CRC and para-tumor tissues were examined, and its oncogenic role was determined using in vitro and in vivo functional assays following genetic manipulation of CRC cells. AKR1B10 was downregulated in CRC tissues compared to the adjacent normal colorectal tissues, and associated with the clinicopathological status of the patients. AKR1B10 depletion promoted the proliferation and migration of CRC cells in vitro , while its ectopic expression had the opposite effect. AKR1B10 was also significantly correlated with FGF1 gene and protein levels. Knockdown of AKR1B10 promoted tumor growth in vivo , and increased the expression of FGF1. Finally, AKR1B10 inhibited FGF1, and suppressed the proliferation and migration ability of CRC cells in an FGF1-dependent manner. In conclusion, AKR1B10 acts as a tumor suppressor in CRC by inactivating FGF1, and is a novel target for combination therapy of CRC.

Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers

“…Eventually, we identified eleven articles published between 2014 and 2020. [ 5 – 15 ] The flow diagram of the selection is displayed in Figure 1 .…”

“…[ 4 ] Recently, an increasing number of studies have explored the association between AKR1B10 expression and prognostic value in digestive system cancers. [ 5 – 15 ] For example, Yao et al, confirmed that low AKR1B10 expression indicated poor prognosis for gastric cancer (GC) and colorectal cancer (CRC). [ 14 , 15 ] Wang et al, also found that high AKR1B10 expression revealed a lower risk of recurrence in patients with hepatocellular carcinoma (HCC).…”

“…[ 5 – 15 ] For example, Yao et al, confirmed that low AKR1B10 expression indicated poor prognosis for gastric cancer (GC) and colorectal cancer (CRC). [ 14 , 15 ] Wang et al, also found that high AKR1B10 expression revealed a lower risk of recurrence in patients with hepatocellular carcinoma (HCC). [ 13 ] However, Fang et al, demonstrated that AKR1B10 was significantly correlated with tumor size, perineural invasion and recurrence, and was a risk factor for poor prognosis in oral squamous cell carcinomas (OSCC).…”

Predicting Non-Alcoholic Fatty Liver Disease Progression and Immune Deregulations by Specific Gene Expression Patterns

“…As storage of retinyl in cytoplasmic lipid droplets is the most distinctive feature of hepatic stellate cell (45), therefore, the abnormal expression of AKR1B10 may lead to the activation of HSC and promote the progression of NAFLD (46). Furthermore, studies have demonstrated that AKR1B10 was also related to tumor growth and metastasis, which may explain the lasting role in NAFL-NASH-HCC progression (47)(48)(49). Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is a secreted glycoprotein that has multiple functions and affects proliferation, differentiation, migration and inflammation (50)(51)(52).…”

Homeobox A5 activates p53 pathway to inhibit proliferation and promote apoptosis of adrenocortical carcinoma cells by inducing Aldo-Keto reductase family 1 member B10 expression

“…A considerable body of evidence indicates that AKR1B10 participates in the occurrence and development multiple cancer, such as nasopharyngeal carcinoma, lung cancer and colorectal cancer [7][8][9]. After searching GEPIA database, we found that AKR1B10 is down-regulated in tissues of ACC patients (Figure 1a).…”