Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

The relationship between cancer associated fibroblasts biomarkers and prognosis of breast cancer: a systematic review and meta-analysis.

Background: To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. Methodology: PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias. Results: Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-ß (PDGFR-ß) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-ß (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-ß expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). Conclusions: The high expression of α-SMA, PDPN, PDGFR-ß in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

Characteristic of persistent human papillomavirus infection in women worldwide: a meta-analysis.

Objectives: We aimed to estimate the genotype distribution of persistent human papillomavirus (HPV) infection in females worldwide, and provided a scientific basis for the prevention strategies of cervical cancer (CC) and the development of HPV vaccines. Methods: Both English and Chinese databases were researched from the inception to July 2023. The pooled persistent HPV infection prevalence was calculated using a random effects model. The subgroup analysis was performed to explore the heterogeneity. Publication bias was evaluated using funnel plot, Egger's and Begg's test. Results: Twenty-eight studies with 27,335 participants were included. The pooled prevalence of persistent HPV infection was 29.37% (95% CI [24.05%∼35.31%]), and the genotypes with the persistent infection prevalence were HPV16 (35.01%), HPV52 (28.19%), HPV58 (27.06%), HPV18 (25.99%), HPV33 (24.37%), HPV31 (23.35%), HPV59 (21.87%), HPV39 (19.54%), HPV68 (16.61%) and HPV45 (15.05%). The prevalence of multiple and single HPV persistent infection were 48.66% and 36.71%, respectively; the prevalence of persistent HPV infection in different age groups (<30, 30∼39, 40∼49, >50) were 29.83%, 28.39%, 22.24% and 30.22%, respectively. The follow-up time was significantly associated with heterogeneity by subgroup analysis (P < 0.05), and the prevalence of persistent infection decreased with longer follow-up time. Conclusions: Multiple infections were more likely to occur persistent HPV infection than single infection. In addition to HPV vaccination, we should emphasize the follow-up management for women under 30 and over 50 years old, those with high-risk HPV infection (HPV59, 39, 68) and multiple infections.

The awareness and acceptance of HPV vaccines among parents of primary and junior high school students in China: a meta-analysis.

The awareness and acceptance of the human papillomavirus (HPV) vaccines among Chinese primary and junior high school students is limited. A meta-analysis was conducted to evaluate the awareness of HPV and HPV vaccines, as well as the acceptance of HPV vaccines, providing evidence-based strategies to promote HPV vaccination. Based on the databases of CNKI, Wanfang, VIP, PubMed, Embase, and Cochrane library, the literatures about the awareness of HPV and HPV vaccines, as well as the acceptance of HPV vaccines among parents of primary and junior high school students were collected from the inception to June 2023. Subgroup analysis was used to find the source of heterogeneity. Publication bias was evaluated using funnel plots and Egger's test. Fifteen literatures with 21,853 participants were included. The pooled HPV awareness, HPV vaccine awareness and acceptance rates among parents of primary and junior high school students in China were 42.90% (95% CI: 33.34%-52.47%), 28.11% (95% CI: 18.20%-43.41%), and 55.29% (95% CI: 45.85%-64.36%), respectively. The survey period and the proportion of female parents were the heterogeneity in awareness of HPV and HPV vaccines, as well as acceptance of HPV vaccines by subgroup analysis. Additionally, regional distribution emerged as another significant source of heterogeneity in HPV vaccine acceptance. The primary cause for parents' reluctance to vaccinate their children was theirs worries about the safety of the vaccines (66.21%). Though the awareness of HPV and its vaccines was low among parents of primary and junior high school students in China, the acceptance of HPV vaccines was relatively high. Strengthening health education and publicity was crucial to enhance awareness and acceptance, promoting HPV vaccination for effective cervical cancer prevention.