Prognostic Evaluation for Oral Squamous Cell Carcinoma:A Novel Method Based on m6A Methylation Regulators

Objective:This study aimed to examine a novel method for prognostic evaluation of patients with oral squamous cell carcinoma(OSCC)based on the expression of heterogeneous nuclear ribonucleoprotein C(HNRNPC),YTH domain-binding protein 2(YTHDF2),and methyltransferase 14(METTL14).Methods:We obtained the RNA sequence and clinical information of OSCC patients from The Cancer Genome Atlas database.An optical method was established by the least absolute shrinkage and selection operator Cox regression algorithm,which was used to calculate the risk score of every sample.In addition,all samples(n=239)were classified into high-risk(n=119)and low-risk(n=120)groups,and the overall survival(OS)time and clinical characteristics were compared between groups.Moreover,bioinformatics analysis was carried out.Gene set enrichment analysis was performed to investigate the signaling pathways of HNRNPC,YTHDF2,and METTL14.Results:The two groups showed significantly different OS time,tumor grades,tumor stages,and pathologic T stages(P<0.05).The receiver operating characteristic analysis identified that our method was effective and it was more accurate than use of age,gender,tumor grade,tumor stage,pathologic T stage,and pathologic N stage in OSCC prognostic prediction.Gene set enrichment analysis revealed that HNRNPC,YTHDF2,and METTL14 were mainly associated with ubiquitin-mediated proteolysis,cell cycle,RNA degradation,and spliceosome signaling pathways.Conclusion:The method based on the expression of HNRNPC,YTHDF2,and METTL14 can predict the prognosis of patients with OSCC independently,and its prognostic value is better than that of clinicopathological characteristic indicators.

RNA modification by M6A methylation in cardiovascular diseases: Current trends and future directions

N6-methyladenosine(M6A)is the most common modification in eukaryotic RNAs for the regulation of RNA transcription,processing,splicing,degradation,and translation.RNA modification by M6A is dynamically reversible,involving methylated transferase,demethylase,and methylated reading protein.M6A-mediated gene regulation involves cell differentiation,metastasis,apoptosis,and proliferation.Dysregulation of M6A can lead to various diseases.Cardiovascular disease(CVD)seriously endangers human health and brings great social burden.Seeking effective prevention and treatment strategies for CVD is a challenge to both fundamentalists and clinicians.Substantial evidence has suggested the key role of M6A modification in the development of CVDs.This review summarizes the mechanism of M6A RNA modification and the latest research progress in respect with its role in CVDs,including atherosclerosis,coronary artery disease,myocardial infarction and cardiac remodeling,myocardial ischemia-reperfusion injury,heart failure,hypertension,and aortic aneurysm,and the potential applications of the findings to CVDs,thereby providing new ideas and approaches for the diagnosis and therapy of CVDs.

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells

Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.

Comprehensive analysis of the prognostic impact and immune implication of KIAA1429 in lung adenocarcinoma

Background:Lung adenocarcinoma(LUAD)is the most common lung cancer worldwide.N6-methyladenosine(m6A)methylation is a messenger RNA(mRNA)modification that plays a key role in tumor growth,immune microenvironment,and immunotherapy response.This study investigated the expression level,mutation status,prognostic value,and predictive ability for response to anti-PD-1 immunotherapy of the m6A methyltransferase KIAA1429 in LUAD.Methods:This study examined multiple public data cohorts and independent samples from National Cancer Center(NCC)to evaluate the clinical significance and prognostic value of KIAA1429 in LUAD using bioinformatics techniques and immunohistochemical staining.We also evaluated the predictive value of KIAA1429 expression for anti-PD-1 immunotherapy efficacy.GSEA analysis was performed using KIAA1429 RNA-seq data at the tumor tissue level and cellular level to explore the potential molecular mechanism.Results:In public databases,KIAA1429 was significantly associated with clinicopathological parameters in LUAD patients and had the potential to predict patient prognosis.The mutation characteristics of KIAA1429-related genes were analyzed and TP53,TTN,CSMD3,and other genes showed high mutation frequencies in LUAD.An independent cohort of 415 samples confirmed that high KIAA1429 expression was significantly associated with poorer prognosis in LUAD patients.Analysis of a small immunotherapy cohort showed that patients with high expression of KIAA1429 had better response after immunotherapy,and the proportion of patients with immunotherapy response was higher in this group.Conclusions:Our study confirmed that KIAA1429 was highly expressed in LUAD and was significantly associated with poor prognosis.Moreover,KIAA1429 may serve as a potential marker to predict the efficacy of immunotherapy in LUAD.