Study On The Mechanisms Of AKR1B10 Regulating Autophagy And Regulating The Expression Of Inflammatory Factors In Human Colon Cancer Cells

Colon cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death.It was estimated that there will be more than 2.2 million new cases of colon cancer and 1.1 million death cases of colon cancer worldwide in 2030.At present,surgery remains the primary choice for the treatment of colon cancer.Meanwhile adjuvant therapy is applied to diminish the rates of local recurrence and improve the rates of survival.However,the five-year survival of colon cancer patients is only about 50%.Therefore,it is necessary to study the mechanism of colon cancer development.Autophagy is considered as an important switch for cell transformation from normal to malignant during colorectal cancer development.Previous research by our group found that the membrane receptor Neuropilin1(NRP1)in colon cancer cells was significantly up-regulated under glucose starvation.It was also found that knockdown of the NRP1 inhibits autophagy and largely upregulates the expression of Aldo-Keto Reductase family 1 B10(AKR1B10).Further research on this subject demonstrated that AKR1B10 interacts with and reduces Glyceraldehyde-3-phosphate dehydrogenase(GAPDH)through which affects the nuclear import of GAPDH,and subsequently represses autophagy.Together,our findings unravel a novel mechanism of AKR1B10 in regulating autophagy through GAPDH.In our studies,we also evaluated the relationship between AKR1B10 expression and clinicopathological characteristics in colon cancer and showed that AKR1B10 expression was significantly correlated with TNM stage and clinical stage of colon cancer.It has been reported that colorectal cancer is closely associated with chronic inflammation and the underlying molecular mechanisms are still elusive.Here we found that knockdown of AKR1B10 significantly decreased the expression of the inflammatory cytokines,IL1α and IL6,induced by lipopolysaccharide(LPS)via inhibiting NF-κB signaling pathway.Furthermore,AKR1B10 depends on its reductase activity to affect the NF-κB signaling pathway and subsequently affect the production of inflammatory cytokines.Collectively,our findings provided important insights into a previously unrecognized role of AKR1B10 in colon cancer.