Abstract
TDO2 is a key enzyme in the kynurenine metabolic pathway, which is the most important pathway of tryptophan metabolism. It has been shown that miRNAs are involved in cell metastasis through interaction with target mRNAs. In this study, we found 645 miRNAs that could be immunoprecipitated with TDO2 through the RNA-immunoprecipitation experiment. miR-126-5p was selected as the research target, which was also confirmed by dual-luciferase reporter assay. Through qRT-PCR analysis, it was verified that the overexpression of miR-126-5p promoted the expression of TDO2, PI3K/AKT and WNT1. Meanwhile, it was verified that overexpression of miR-126-5p can promote intracellular tryptophan metabolism by HPLC. We also verified the effects of miR-126-5p on cell proliferation, migration, and invasion by cck-8, cell colony formation and trans-well assay in both HCCLM3 cells and HepG2 cells. In vivo experiments were also conducted to verify that miR-126-5p promoted tumor formation and growth via immunohistochemical detection of cell infiltration and proliferation to generate markers Ki-67, BAX, and VEGF. In conclusion, our results suggest that miR-126-5p is a biomarker and a potential new treatment target in the progression of HCC via promoting the expression of TDO2.
Highlights
IntroductionHCC (hepatocellular carcinoma) is a serious threat to health and one of the most common gastrointestinal malignancies, with the third highest mortality rate [1]
HCC is a serious threat to health and one of the most common gastrointestinal malignancies, with the third highest mortality rate [1]
RNA sequencing was performed to screen out the RNA that could bind to TDO2
Summary
HCC (hepatocellular carcinoma) is a serious threat to health and one of the most common gastrointestinal malignancies, with the third highest mortality rate [1]. 383,000 people in China die of liver cancer every year, which accounts for 51% of all liver cancer deaths in the world [2]. A variety of strategies have been used to treat HCC, such as liver transplantation, liver resection, radiofrequency ablation, and transarterial chemoembolization, the prognosis of HCC is still poor because of tumor invasion, frequent intrahepatic spread, and extrahepatic metastasis [3]. It is necessary to find candidate therapeutic targets, and to improve the quality of life of HCC patients. TDO2 (tryptophan 2,3-dioxygenase) is a key enzyme in the tryptophan-kynurenine metabolic pathway. The human TDO2 protein contains 406 amino acids; it is encoded by TDO2 gene on chromosome 4, with a length of 65,669 bp, including 12 exons and
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