ABSTRACT
Cervical cancer (CC) is one of the leading cancers among the female reproductive system. The piwi-interacting RNA (piRNA) function and biogenesis has been studied in various cancers, including CC. But the precise mechanism of piRNA in CC is still unknown. In our study, we found that piRNA-17458 was overexpressed in CC tissues and cells. piRNA-17458 mimic and inhibitor promoted and suppressed proliferation, migration and invasion ability of CC cells, respectively. We also demonstrated that piRNA-17458 mimic could contribute to tumor growth in mice xenograft models. Besides, we also found that the piRNA-17458 mimic could enhance mRNA N6-methyladenosine(m6A) levels and increase WTAP stability in CC cells, while the effects of the mimic was reversed by the WTAP knockdown. The results of dual luciferase reporter assay showed that WTAP was a direct target of piRNA-17458. Knockdown of WTAP attenuated proliferation, migration and invasion of CC cells in piRNA-17458 mimic group. Our finding not only demonstrates for the first time that piRNA-17458 is overexpressed in CC tissues and cells, but also shows that piRNA-17458 promotes tumorigenesis of CC in a WTAP-mediated m6A methylation manner.
ABSTRACT
Background: ANGPTL3, 4 and 8 have been reported to be involved in the regulation of lipid and glucose metabolism. The aim of this study was to investigate the expression of ANGPTL3, 4, 8 in hypertensive patients with or without overweight/obesity, T2D, and hyperlipidemia, and the possible association between their expression and the status of the aforementioned comorbidities. Methods: Plasma levels of ANGPTL3, 4, and 8 in 87 hospitalized patients with hypertension were measured using ELISA kits. Associations between circulating ANGPTLs levels and the most common additional cardiovascular risk factors were assessed using multivariate linear regression analyses. Pearson's correlation analysis was used to examine the association between ANGPTLs and clinical parameters. Results: In the context of hypertension, (1) although not statistically significant, circulating ANGPTL3 levels were higher in the overweight/obese group than in the normal weight group; (2) circulating levels of ANGPTL3 and ANGPTL8 were significantly lower in patients with T2D than in non-diabetic patients; (3) circulating ANGPTL3 levels were significantly higher in the hyperlipidemic group than in the non-hyperlipidemic group. ANGPTL3 was associated with T2D and hyperlipidemia status, whereas ANGPTL8 was independently associated with T2D status. In addition, circulating ANGPTL3 levels were positively correlated with TC, TG, LDL-C, HCY, and ANGPTL8, and circulating ANGPTL4 levels were positively correlated with UACR and BNP. Conclusion: Changes in circulating ANGPTL3 and ANGPTL8 levels have been observed in hypertensive patients with the most common additional cardiovascular risk factors, suggesting a role in the common comorbidities of hypertension and cardiovascular disease. Hypertensive patients with overweight/obesity or hyperlipidemia may benefit from therapies targeting ANGPTL3.
