HPV16 E6-induced M2 macrophage polarization in the cervical microenvironment via exosomal miR-204-5p.

The persistent infection of high-risk human papillomavirus (HPV) and the progression of cervical cancer necessitate the involvement of microenvironmental immunity. As cervical lesions advance, there is an observed increase in the infiltration of type 2 (M2) macrophages. However, the precise mechanism driving this increased infiltration of M2 macrophages remains unclear. In this study, we investigated the role of exosomes in polarising M2 macrophages in cervical lesions associated with HPV E6. Through the analysis of bioinformatics data and clinical specimens, we discovered a positive correlation between HPV E6/E7 mRNA copy number and the level of M2 macrophage infiltration. Exosomes derived from HPV E6 overexpressed (HPV E6+) cervical squamous cell carcinoma (CESC) cells were found to induce the polarisation of macrophages towards M2 type. Specifically, miR-204-5p, enriched in HPV E6 + CESC exosomes, was transported into macrophages and triggered M2 macrophage polarisation by inhibiting JAK2. The clinical relevance of exosomal miR-204-5p in the progression of cervical lesions was validated through serum samples from 35 cases. Exosomal miR-204-5p emerges as a critical factor influencing M2 macrophage polarisation and is correlated with the severity of cervical lesions. Consequently, miR-204-5p could be used as a potential treatment and a candidate biomarker for cervical lesions.

Update on the association of miR-149 rs2292832 C>T polymorphism with gastric cancer risk: A meta-analysis study of gastrointestinal cancers.

OBJECTIVE: Single nucleotide polymorphisms in microRNAs are believed to affect the occurrence and progression of cancer by altering the expression and biological functions of microRNAs. Several studies investigated the role of the miR-149 rs2292832 C>T polymorphism on the risk of gastric cancer (GC), but got conflicting results. METHODS: We performed a comprehensive and systematic search through the PubMed MEDLINE, Google Scholar, Science Direct, Scopus, CNKI, and Web of science, 8 studies were included in the meta-analysis to determine whether miR-149 rs2292832 C>T polymorphism contributed to the risk of GC. RESULTS: Pooled data indicated that miR-149 rs2292832 C>T polymorphism was not associated with GC risk. In the stratified analysis by ethnicity, miR-149 rs2292832 C>T polymorphism significantly increased GC risk under the allele comparison model (odds ratio [OR] = 1.27, 95% CI = 1.04-1.55, Pheterogeneity = 0.18, P = .02), recessive model (OR = 1.44, 95% CI = 1.04-2.01, Pheterogeneity = 0.19, P = .03) among Caucasians; but decreased GC risk under the allele comparison model (OR = 0.89, 95% CI = 0.81-0.98, Pheterogeneity = 0.22, P = .02) and dominant model (OR = 0.82, 95% CI = 0.72-0.93, Pheterogeneity = 0.15, P = .01) among Asian. CONCLUSION: Our meta-analysis suggests a positive correlation between miR-149 rs2292832 C>T polymorphism and GC development among Caucasians, but negative correlation among Asian population.

MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis.

OBJECTIVE: The methionine synthase reductase (MTRR) gene encodes the MTRR enzyme involved in the metabolic pathway of homocysteine. Several studies investigated the effect of the MTRR rs1532268 gene polymorphism on the risk of gastric cancer (GC), but the results have been inconsistent. METHODS: We performed a comprehensive and systematic search of PubMed, Google Scholar, MEDLINE, Science Direct, Scopus, CNKI, and Web of Science. Five studies were included in this meta-analysis to determine whether MTRR rs1532268 polymorphism contributes to the risk of GC. RESULTS: Pooled data indicated that the MTRR rs1532268 polymorphism significantly increased GC risk under the allele comparison model (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01-1.29) and dominant model (OR = 1.14, 95% CI = 1.00-1.30). In the analysis stratified by ethnicity, no relationship was found in Whites or Asians. CONCLUSION: Our meta-analysis suggests a positive correlation between MTRR rs1532268 polymorphism and GC development.

A multivariate modeling method for the prediction of low fetal fraction before noninvasive prenatal testing.

OBJECTIVE: To investigate factors associated with fetal fraction and to develop a new predictive method for low fetal fraction before noninvasive prenatal testing. METHODS: The study was a retrospective cohort analysis based on the results of noninvasive prenatal testing, complete blood count, thyroxin test, and Down's syndrome screening during the first or second trimester in 14,043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction status (fetal fraction < 4%) through individual information and laboratory records. The performance of the model was evaluated and compared to predictions using maternal weight. RESULTS: Of 14,043 cases, maternal weight, red blood cell, hemoglobin, and free T3 were significantly negatively correlated with fetal fraction while gestation age, free T4, pregnancy-associated plasma protein-A, alpha-fetoprotein, unconjugated estriol, and ß-human chorionic gonadotropin were significantly positively correlated with fetal fraction. Compared to predictions using maternal weight as an isolated parameter, the model had a higher area under the curve of receiver operating characteristic and overall accuracy. CONCLUSIONS: The comprehensive predictive method based on combined multiple factors was more effective than a single-factor model in low fetal fraction status prediction. This method can provide more pretest quality control for noninvasive prenatal testing.

Prostatectomy Versus Observation for Localized Prostate Cancer: A Meta-Analysis.

BACKGROUND AND AIMS: Controversy exists regarding whether prostatectomy benefits localized prostate cancer patients; the aim of our study was to evaluate the role of prostatectomy in localized prostate cancer patients. MATERIALS AND METHODS: A systematic search was conducted using PubMed and Web of Science through March 22, 2019, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify randomized studies reporting on prostatectomy for localized prostate cancer patients. RESULTS: Of a total of 1827 studies, six were considered for evidence synthesis. A total of 2524 patients in 3 studies were included for survival analysis, where 1256 patients received prostatectomy and 1268 patients received no treatment but were regularly followed up. Three other studies were included for adverse effects analysis. Prostatectomy displayed a significantly decreased risk of death of 9% compared with that of observation for patients with localized prostate cancer (risk ratio = 0.91; 95% confidence interval, 0.85-0.97; p = 0.007). Pooled data indicated that prostatectomy reduced the risk of disease progression by 43% (risk ratio = 0.57; 95% confidence interval, 0.47-0.70; p < 0.00001). Anxiety, depressed mood, well-being, and sense of meaningfulness for patients were not different between the prostatectomy and observation groups. However, prostatectomy increased the risk of erectile dysfunction by 2.10-fold (risk ratio = 2.10; 95% confidence interval, 1.36-3.26; p = 0.0009) and the risk of urinary function problems by 2.02-fold (risk ratio = 2.02; 95% confidence interval, 1.15-3.54; p = 0.01). CONCLUSION: Prostatectomy prolonged survival and deferred disease progression compared to observation for patients with localized prostate cancer. Symptoms between the two groups were not significantly different except for erectile and urinary function. Patients should decide on prostatectomy after balancing the survival benefit and risk of erectile dysfunction.

Crosstalk between Meg3 and miR-1297 regulates growth of testicular germ cell tumor through PTEN/PI3K/AKT pathway.

Maternally Expressed Gene 3 (Meg3) encodes a long non-coding RNA that has been recently shown to regulate tumorigenesis through its interaction with microRNA (miR). We have recently reported that miR-1297 might play a role in the regulation of PTEN/PI3k/Akt signaling pathway in testicular germ cell tumor (TGCT). However, a crosstalk between Meg3 and miR-1297 in TGCT has not been appreciated. Here, we analyzed the levels of Meg3, miR-1297 and PTEN in TGCT specimens, compared to paired adjacent non-tumor tissue (NT), and found that Meg3 levels were significantly decreased and miR-1297 levels were unchanged in TGCT. PTEN protein but not mRNA levels significantly decreased in TGCT. Bioinformatics analyses showed that miR-1297 bound to 3'-UTR of PTEN mRNA, while miR-1297 also bound to Meg3. Luciferase report assay showed that Meg3 overexpression abolished the effects of miR-1297 on 3'-UTR of PTEN mRNA, possibly through competitive binding, which was supported by double fluorescent in situ hybridization showing co-localization of intracellular Meg3 and miR-1297 signals in TGCT cells. Moreover, Meg3 overexpression abolished the inhibitory effects of miR-1297 on PTEN, resulting in deactivation of Akt and decreases in cell growth. Together, these data demonstrate a previous unappreciated pathway in which Crosstalk between Meg3 and miR-1297 regulates growth of TFCT through PTEN/PI3K/AKT signaling. Re-expression of Meg3 may be an attractive strategy for TGCT therapy.

Rice ethylene-response AP2/ERF factor OsEATB restricts internode elongation by down-regulating a gibberellin biosynthetic gene.

Plant height is a decisive factor in plant architecture. Rice (Oryza sativa) plants have the potential for rapid internodal elongation, which determines plant height. A large body of physiological research has shown that ethylene and gibberellin are involved in this process. The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF) family of transcriptional factors is only present in the plant kingdom. This family has various developmental and physiological functions. A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering and panicle branching) was cloned from indica rice variety 9311. Bioinformatic analysis suggested that this ERF has a potential new function. Ectopic expression of OsEATB showed that the cross talk between ethylene and gibberellin, which is mediated by OsEATB, might underlie differences in rice internode elongation. Analyses of gene expression demonstrated that OsEATB restricts ethylene-induced enhancement of gibberellin responsiveness during the internode elongation process by down-regulating the gibberellin biosynthetic gene, ent-kaurene synthase A. Plant height is negatively correlated with tiller number, and higher yields are typically obtained from dwarf crops. OsEATB reduces rice plant height and panicle length at maturity, promoting the branching potential of both tillers and spikelets. These are useful traits for breeding high-yielding crops.