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.

Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3′-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 increased G6PD expression in cervical cancer cells. Regression analysis revealed that miR-1 levels correlate negatively with the clinicopathologic features in HR-HPV 16/18-infected cervical cancer patients. miR-1 overexpression inhibited proliferation and promoted apoptosis in cervical cancer cells and reduced xenograft tumor growth in nude mice. Conversely, sponge-mediated miR-1 knockdown markedly increased viability and reduced apoptosis in cervical cancer cells and supported neoplasm growth. Restoration of G6PD expression partially reversed the effects of miR-1 overexpression both in vitro and in vivo. In addition, co-transfection of G6PD siRNA and miR-1 sponge partially reversed miR-1 sponge-induced reductions in cell viability and neoplasm growth. These results suggest that miR-1 suppresses the development and progression of HR-HPV 16/18-infected cervical cancer by targeting G6PD and may be a promising novel therapeutic candidate.

Recent evidences revealed that the alteration of microRNAs (miRNAs) might be associated with neuroplasticity induced by voluntary running wheel (RW) exercise in mice suffered from traumatic brain injury (TBI). In the present study, we explored the possible role of miR21 involved in the cognitive improvement following voluntary RW in TBI mice. Firstly, in situ hybridization and quantitative real-time PCR (qRT-PCR) were employed to determine the hippocampal expression and location of miR21 in TBI mice with or without spontaneous RW. Either miR21-mimics/plenti-miR21 or miR21-agomir/miR21-sponge was employed to regulate the miR21 expression in vivo and in vitro. Acquisition of spatial learning and memory retention was assessed by Morris Water Maze (MWM) test. Golgi stain was also performed to evaluate the alteration of hippocampal dendrite. Our finding confirmed that the elevated miR21 level in hippocampal post-TBI was significantly reduced by spontaneous RW. Overexpression of miR21 in TBI mice with spontaneous RW induced deteriorations in spatial learning and memory retention by significant decreases in the somata size and branch points of the hippocampus neurons. In vitro transduction with miR21 also reduced the neurite extension and the area of cultured hippocampal neuron. However, miR21 down-regulation reversed these effects. The present data strongly suggest that miR21 is an important molecule that has been involved in neuroprotection induced by voluntary RW exercise post-TBI.

Elevated brain activation, or hyperexcitability, induces cognitive impairment and confers an increased risk of Alzheimer's disease (AD). Blocking the overexcitation of the neural network may be a promising new strategy to prevent, halt, and even reverse this condition. Physical exercise has been shown to be an effective cognitive enhancer that reduces the risk of AD in elderly individuals, but the underlying mechanisms are far from being fully understood. We explored whether long-term treadmill exercise attenuates amyloid precursor protein (APP)/presenilin-1 (PS1) mutation-induced aberrant network activity and thus improves cognition by altering the numbers and/or distribution of voltage-gated sodium channels (Nav) in transgenic mice. APP/PS1 mice aged 2, 3.5, 5, 6.5, 8, and 9 months underwent treadmill exercise with different durations or at different stages of AD. The alterations in memory, electroencephalogram (EEG) recordings, and expression levels and distributions of Nav functional members (Nav1.1α, Nav1.2, Nav1.6, and Navβ2) were evaluated. The results revealed that treadmill exercise with 12and 24-week durations 1) induced significant improvement in novel object recognition (NOR) memory and Morris water maze (MWM) spatial memory; 2) partially reduced abnormal spike activity; and 3) redressed the disturbed cellular distribution of Nav1.1α, aberrant Navβ2 cleavage augmentation, and Nav1.6 upregulation. Additionally, APP/PS1 mice in the 24-week exercise group showed better performance in the NOR task and a large decrease in Nav1.6 expression, which was close to the wild-type level. This study suggests that exercise improves cognition and neural activity by altering the numbers and distribution of hippocampal Nav in APP/PS1 mice. Long-term treadmill exercise, for about 24 weeks, starting in the preclinical stage, is a promising therapeutic strategy for preventing AD and halting its progress.

Cervical cancer, which is significantly associated with high-risk human papillomavirus (HPV) infection, currently ranks the fourth most common cancer among women worldwide. Previous literature reported that the elevated expression of G6PD was significantly correlated with the occurrence and deterioration of human cervical cancer, especially with the cervical cancer with HPV16 and HPV18 infection. In this study, we verified that G6PD expression has a strong positive correlation with HPV16 E6 levels in cervical cancer tissues and cells. In addition, regulating the expression of HPV16 E6 significantly affected the proliferation, apoptosis, migration, and invasion in the cervical cancer HeLa cells, as well as the transcript and protein levels of G6PD. The luciferase reporter assay and ChIP assay proved that HPV16 E6 stimulated the transcription of G6PD mRNA and subsequently enhanced the expression of G6PD through directly binding to the specific sites in the promoter of G6PD. Our findings reveal that HPV16 E6 is a novel regulatory factor of G6PD. Furthermore, by regulating the expression of G6PD, HPV16 E6 might promote the proliferation and migration potential, and inhibit apoptosis of cervical cancer cells, which ultimately contributed to the progression and metastasis of cervical cancer.