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Novel evidence for oncogenic piRNA-823 as a promising prognostic biomarker and a potential therapeutic target in colorectal cancer.


ABSTRACT: piRNA-823 as a member of the piRNA family is reported to promote tumour cell proliferation in multiple myeloma and hepatocellular cancer. However, few studies on the function of piRNA-823 in colorectal cancer (CRC). Our present study data showed that piRNA-823 plays an oncogene role in CRC cells. Inhibition of piRNA-823 can significantly inhibit the proliferation, invasion and apoptosis resistance of CRC cells. Mechanism studies have shown that piRNA-823 inhibits the ubiquitination of hypoxia-inducible factor-1 alpha (HIF-1?) by up-regulating the expression of Glucose-6-phosphate dehydrogenase (G6PD) and ultimately up-regulates the glucose consumption of carcinoma cells and inhibits the content of intracellular reactive oxygen species (ROS). Therefore, we speculate piRNA-823 promotes the proliferation, invasion and apoptosis resistance of CRC cells by regulating G6PD/HIF-1? pathway. In this study, we set up the cancer-promoting function recovery experiment of piRNA-823 by silencing G6PD gene to confirm the dominance of the above-mentioned pathways. Using clinical samples, we found that overexpression of piRNA-823 correlated with poor overall survival and predicted a poor response to adjuvant chemotherapy of patients with CRC. In a word, our research has further enriched the theory of piRNA-823 promoting the progression of CRC, and laid a solid foundation for the development of piRNA-823-based gene therapy for CRC and its use as a promising prognostic biomarker in CRC patients.

SUBMITTER: Feng J 

PROVIDER: S-EPMC7417729 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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