Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124.

Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels. Moreover, we demonstrate that miR-124, directly targeting iASPP, reduces expression of iASPP and attenuates CC cell growth and invasiveness. Low miR-124 expression is inversely correlated with increased expression of iASPP mRNA in CC tissues. In a cohort of 40 patients with CC, the low miR-124 expression was correlated with poor 5-year overall survival (P = 0.0002) and shorter disease-free survival 5-year (P = 0006). Treatment with the DNA methyltransferase inhibitor Zebularine increases miR-124 expression and retards CC cell growth and invasion with minimal toxicity to normal cells. Even at a non-toxic concentration, Zebularine was effective in suppressing CC cell invasion and migration. Altogether, the restoration of miR-124 reduces iASPP expression and leads to p53-dependent tumor suppression, suggesting a therapeutic strategy to treat iASPP-associated CC.

HPV self-sampling in Japanese women: A feasibility study in a population with limited experience of tampon use.

OBJECTIVES: Cervical cancer incidence and mortality is increasing in Japanese women under age 50. Screening uptake is low and proactive recommendations for human papillomavirus vaccination have been suspended. Other cervical cancer prevention initiatives are urgently needed. We assessed whether human papillomavirus self-sampling might be an acceptable alternative to physician-led screening, particularly in women with limited experience of tampon use. We also sought to identify any practical, logistical, or safety issues in women already attending for screening, before carrying out further large-scale studies in non-responders. METHODS: In total, 203 women aged 20-49 attending their annual workplace healthcheck in Sapporo, northern Japan, performed unsupervised human papillomavirus self-sampling before undergoing a physician-led cervical smear and human papillomavirus test, and completing a measure of acceptability for both tests. RESULTS: Ninety per cent of participants stated they would use self-sampling again. They found instructions easy to follow and reported no issues with the usability of the self-sampling device. Compared with physician-led testing, women found self-sampling significantly less painful, less embarrassing and could relax more (p < 0.001), regardless of history of tampon use, which was associated with negative experiences in physician sampling (p = 0.034). Women lacked confidence the test had been performed correctly, despite no unsatisfactory samples. No safety issues were reported. CONCLUSIONS: Self-sampling was highly acceptable in this population of women. They could perform the test safely unsupervised, but lacked confidence the test has been carried out correctly. Japanese women need to be educated about the accuracy of human papillomavirus self-sampling and further large-scale studies are necessary in non-responders.