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-1α) 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-1α 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.

• Authors: Junlan Feng, Muqing Yang, Qing Wei, Feifei Song, Youhua Zhang, Xiaodong Wang, Bin Liu, Jiyu Li
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 16 Pg. 9028-9040 (08 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32596991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Tumor
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Small Interfering
• Reactive Oxygen Species

Topics

• Apoptosis (genetics)
• Biomarkers, Tumor (genetics)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, pathology)
• Gene Expression Regulation, Neoplastic (genetics)
• HCT116 Cells
• HEK293 Cells
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Oncogenes (genetics)
• Prognosis
• RNA, Small Interfering (genetics)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (genetics)
• Up-Regulation (genetics)