METTL3 promotes the growth and metastasis of pancreatic cancer by regulating the m6A modification and stability of E2F5.

BACKGROUND: Pancreatic cancer belongs to lethal cancer with limited efficient treatment currently, and its main cause of death is rapid tumor growth and early metastasis. N6-methyladenosine (m6A) modification is a new method of epigenetic gene regulation involved in tumor progression, in which methyltransferase-like 3(METTL3) is the sole catalytic subunit. However, the role of METTL3 in pancreatic cancer remains to be explored. METHODS: m6A level was measured using MeRIP assay, and RT-qPCR and western blot were applied to determine mRNA and protein expression, respectively. Cellular behaviors were detected using CCK-8, EdU, wound healing and transwell assays. Xenograft assays were conducted to further verify the roles of METTL3 in pancreatic cancer. RESULTS: METTL3 was highly expressed in pancreatic cancer. However, downregulation of METTL3 restrained the viability, migration and invasion of pancreatic cancer cells. Moreover, E2F5 was found to be positively regulated by METTL3. Intriguingly, the anti-tumor functions of METTL3 knockdown in the phenotype of pancreatic cancer cells were overturned by overexpression of E2F5. Silencing METTL3 resulted in the decreased stability of E2F5 by methylating E2F5. CONCLUSIONS: In conclusion, METTL3 can promote the malignant progression of pancreatic cancer by modifying E2F5 through m6A methylation to promote its stability.

The influence process of sarcopenia on female cancer: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is one of the early pathological manifestations of cancer cachexia. This change in quality and function has a general and special impact on the prognosis of many types of tumors. However, there are few studies to evaluate the overall impact of sarcopenia on the prognosis of gynecological tumors in sufficient follow-up period. METHODS: This study systematically searched PubMed, EMBASE, web of science, and MEDLINE databases for related studies and related references since April 15, 2021. The 1-year, 5-year overall survival (OS), progression-free survival (PFS), hazard ratio (HR), and 95% confidence interval (CI) were analyzed by Stata 14.0.(CRD 42021236036). RESULTS: A total of 23 observational studies involving 3495 female patients were included in the analysis, with an average prevalence of 46.9% (38.5%-55.3%). Meta-analysis showed that the 1-year OS (RR: 1.60, 95% CI = [1.04, 2.46]) of patients with sarcopenia was significantly lower than that of patients without sarcopenia, and then this effect gradually decreased. The results showed that sarcopenia was an independent predictor of OS (HR: 1.78, 95% CI = [1.38, 2.30]) and PFS (HR: 1.32, 95% CI = [1.02, 1.70]) in gynecological cancer patients. Subgroup analysis showed that sarcopenia was significant in Asian population (HR: 1.93, 95% CI = [1.18, 3.17]) and cervical cancer patients (HR: 5.07, 95% CI = [2.82, 9.56]). CONCLUSION: The survival and recurrence outcome of patients with sarcopenia independently related to surgery, and its impact is very obvious in the short term. In addition, Asian participants with sarcopenia face a greater risk of death than Western participants.

Tao-Hong-Si-Wu Decoction promotes angiogenesis after cerebral ischaemia in rats via platelet microparticles.

Platelet microparticles (PMPs) are membrane particles derived from the platelet membrane that enter into the blood circulation. We sought to explore the therapeutic effects of Tao-Hong-Si-Wu Decoction (THSWD) on angiogenesis in a rat model of cerebral ischaemia-reperfusion (I/R). The protective effect of THSWD on I/R rats was observed morphologically by immunohistochemical expression of VEGF and CD34, along with immunofluorescence results of co-expression of BrdU and vWF. Then, PMPs from different groups of rats were extracted, and cytokine array analysis was used to screen for angiogenesis associated proteins. The results showed that THSWD can promote the expression of VEGF, CD34, BrdU and vWF. Cytokine array analysis revealed the changes in the expression of 29 related angiogenic proteins in the total protein of PMPs, which involved the Notch signalling pathway. Compared with model group, the expression levels of NICD and Hes-1 in the THSWD group were significantly increased. In the context of I/R, the angiogenesis-related proteins of PMPs are different. THSWD may involve the promotion of activation of the Notch signalling pathway to achieve therapeutic effects on cerebral ischaemia.