Cervicovaginal microbiota long-term dynamics and prediction of different outcomes in persistent human papillomavirus infection.

Persistent human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer, posing serious threats to the health of women. Although the cervicovaginal microbiota is strongly associated with CIN, the dynamics of the microbiota during CIN development are unknown. In this retrospective cohort study, we analyzed 3-year longitudinal data from 72 patients diagnosed with a persistent HPV infection almost all caused by high-risk HPV types. Patients were categorized into groups with HPV persistent infection (n = 37), progression to CIN (n = 16), and CIN regression (n = 19) based on infection outcome during the follow-up period. Furthermore, 16S rRNA gene sequencing was performed on consecutively collected cervical samples to explore the composition and dynamics of the cervicovaginal microbiota during the development and regression of CIN. Our results showed that the composition of the cervicovaginal microbiota varied among women with different HPV infection outcomes and remained relatively stable during the follow-up period. Notably, the serial follow-up data showed that these microbial alterations were present for at least 1-2 years and occurred before pathologic changes. In addition, microbial markers that were highly discriminatory for CIN progression or regression were identified. This study provides evidence for a temporal relationship between changes in the cervicovaginal microbiota and the development of CIN, and our findings provide support for future microbial intervention strategies for CIN.

The long non-sacoding RNA TMEM147-AS1/miR-133b/ZNF587 axis regulates the Warburg effect and promotes prostatic carcinoma invasion and proliferation.

BACKGROUND: The Warburg effect is a characteristic tumor cell behavior regarded as one of the cancer hallmarks and promotes tumor progression by promoting glucose uptake and lactate production. Long non-coding RNAs (lncRNAs) had been reported to emerge as a vital function in cancer development. The present research is designed to investigate the underlying molecular mechanism of lncRNA TMEM147 antisense RNA 1 (TMEM147-AS1) on aerobic glycolysis in prostatic carcinoma. METHODS: lncRNA TMEM147-AS1, miR-133b and ZNF587 levels in prostatic carcinoma tissues and cells were detected by a polymerase chain reaction or western blot assays. Cell viability or invasion was determined by Edu (i.e. 5-ethynyl-2'-deoxyuridine), MTT (i.e. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) or transwell assays. Hematoxylin and eosin and immunohistochemical staining were applied for histopathological examination. Tumor xenograft model was employed to investigate tumor growth in vivo. The combinative relationship between TMEM147-AS1 or ZNF587 and miR-133b was confirmed by a luciferase reporter assay. RESULTS: TMEM147-AS1 and ZNF587 were up-regulated in prostatic carcinoma tissues and cells. Knockdown of TMEM147-AS1 or ZNF587 within prostate cancer cells significantly restrained cell viability, invasion and aerobic glycolysis in vitro and suppressed the neoplasia of prostatic carcinoma in vivo. miR-133b was directly targeted in both TMEM147-AS1 and ZNF587. Overexpression of miR-133b restrained prostate cancer cell viability, invasion and aerobic glycolysis. TMEM147-AS1 competitively targeted miR-133b, therefore counteracting miR-133b-mediated repression on ZNF587. CONCLUSIONS: TMEM147-AS1 plays a tumor-promoting action in prostatic carcinoma aerobic glycolysis via affecting the miR-133b/ZNF587 axis, therefore regulating prostatic carcinoma cells invasion and proliferation. These outcomes implied that TMEM147-AS1 could be an effective treatment strategy for further study of prostatic carcinoma.