Elevated glucose-6-phosphate dehydrogenase expression in the cervical cancer cases is associated with the cancerigenic event of high-risk human papillomaviruses

Abstract

The most important etiologic agent in the pathogenesis of cervical cancers (CCs) is human papillomavirus (HPV), while the mechanisms underlying are still not well known. Glucose-6-phosphate dehydrogenase (G6PD) is reported to elevate in various tumor cells. However, no available references elucidated the correlation between the levels of G6PD and HPV-infected CC until now. In the present study, we explored the possible role of G6PD in the pathology of CC induced by HPV infection. Totally 48 patients with HPV + CC and another 63 healthy women enrolled in the clinical were employed in the present study. Overall, prevalence of cervical infection with high-risk-HPV (HR-HPV) type examined was HPV-16, followed by HPV-18. The expressions of G6PD in CC samples were also detected by immunohistochemistry (IHC), qRT-PCR, and Western blot. Regression analysis showed elevated G6PD level was positively correlated with the CC development in 30-40 aged patients with HR-HPV-16/18 infection. The HPV16 + Siha, HPV18 + Hela, and HPV-C33A cell lines were employed and transfected with G6PD deficient vectors developed in vitro. MTT and flow cytometry were also employed to determine the survival and apoptosis of CC cells after G6PD expressional inhibition. Our data revealed that G6PD down-regulation induced poor proliferation and more apoptosis of HPV18 + Hela cells, when compared with that of HPV16 + Siha and HPV-C33A cells. These findings suggest that G6PD expressions in the HR-HPV + human CC tissues and cell lines play an important role in tumor growth and proliferation.

G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma

“…Whelming evidence has demonstrated that G6PD can regulate cell apoptosis in many human tumors. Hu et al found that G6PD downregulation induced cell apoptosis of HPV18+HeLa cells [9]. G6PD knockdown prolonged MAPK activation and increased the susceptibility of H 2 O 2 -mediated cell apoptosis in HepG2 cells [50].…”

“…G6PD harbors two key biological roles, one is to yield ribose-5-phosphate via PPP, which is essential for biosynthesis of nucleic acid in rapidly proliferating cells [15,16]; the other is to produce NADPH, which can promote glycolysis [17], and higher rate of glycolysis in tumor cells produces increasing metabolic rate [18] and thus facilitates tumor survival and growth. Currently, increasing evidence has demonstrated that G6PD is exhibited at high level in many human tumors, including cervical cancer [9], gastric carcinoma [19], leukemia [20], etc. Importantly, G6PD may be a novel biomarker and potential therapeutic target for tumors [21].…”

“…Glucose-6-phosphate dehydrogenase (G6PD), the first and key rate-limited enzyme of PPP, recently, has been verified to Xin Wang, Hongtao Liu and Xiaqing Zhang contributed equally to this work. be closely associated with tumor development and progression [9][10][11]. G6PD, an X-linked gene, consists of 13 exons and 12 introns and encodes 515 amino acids [12][13][14].…”

Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

“…These results imply that G6PD can act as a tumor driver gene 7. Recently, accumulated evidences reveal that elevated G6PD expression or activities have been found in a series of human cancers, including ovarian cancer 8, breast cancer 9, cervical carcinoma 10, prostate cancer 11, bladder cancer 12, etc. Moreover, G6PD overexpression is closely related to the progression of gastric cancer 13 and breast carcinoma 9, and also might be regarded as an independent predictor of poor prognosis for these cancers.…”

G6PD deficiency is associated with renal impairment in T2DM

“…It is an essential component of antioxidant system 4 . Various diseases have been linked to oxidative stress and de ciency of G6PD [16][17][18][19][20][21] . This comparative study addresses association of G6PD de ciency, T2DM, and renal impairment.…”