15P N6-Methyladenosine modification of YY1 mRNA promotes cervical cancer tumorigenesis

BackgroundRecent studies have indicated that N6-methyladenosine (m6A) methylation modification and regulators play a critical role in human cancers. However, the possible functions of m6A and its regulators on cervical cancer (CC) tumorigenesis are still unclear. This study explored the function and mechanism of METTL3 (methyltransferase-like 3) and its downstream target oncogenes in CC.MethodsFirst, we investigated the expression of m6A regulator gene (METTL3) mRNA and proteins by qRT-PCR and western blot assays in cervical cancer cell lines. In addition, we performed a series of functional studies to investigate the oncogenic role of METTL3 and its downstream target oncogenes in CC cells. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to screen the target genes of METTL3. m6A level of mRNA was measured by an m6A-RNA methylation quantification kit.ResultsThe level of m6A RNA methylation was significantly increased in CC cells. METTL3 is a major catalytic enzyme involved in the abundant m6A RNA modification and plays an important role in carcinogenesis. We observed that METTL3 expression was frequently up-regulated in CC cell lines. Functional studies with METTL3 knockdown in CC cells dramatically inhibited cellular proliferation, migratory potential and colony formation abilities. Mechanistically, MeRIP-seq illustrated that Yin-Yang 1 (YY1) as a target of METTL3. Recent studies reported that YY1 is highly expressed in different types of cancer, whereby it is associated with cell proliferation, metastasis, survival, metabolic reprogramming, and poor patient survival. The TCGA data analysis revealed that YY1 mRNA and protein were highly expressed cervical cancer tissues. In addition, Pearson correlation analysis showed that highly expressed METTL3 was positively correlated with YY1 expression. Thus, the METTL3/m6A/YY1 axis promotes cervical carcinogenesis.ConclusionsTaken together, our findings demonstrated the oncogenic role of METTL3 in cervical cancer by regulating YY1 expression in an m6A-dependent manner and provide a new insight into the pathogenesis of CC. Hence, METTL3/m6A/YY1 axis represents a potential target for CC therapy.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. BackgroundRecent studies have indicated that N6-methyladenosine (m6A) methylation modification and regulators play a critical role in human cancers. However, the possible functions of m6A and its regulators on cervical cancer (CC) tumorigenesis are still unclear. This study explored the function and mechanism of METTL3 (methyltransferase-like 3) and its downstream target oncogenes in CC. Recent studies have indicated that N6-methyladenosine (m6A) methylation modification and regulators play a critical role in human cancers. However, the possible functions of m6A and its regulators on cervical cancer (CC) tumorigenesis are still unclear. This study explored the function and mechanism of METTL3 (methyltransferase-like 3) and its downstream target oncogenes in CC. MethodsFirst, we investigated the expression of m6A regulator gene (METTL3) mRNA and proteins by qRT-PCR and western blot assays in cervical cancer cell lines. In addition, we performed a series of functional studies to investigate the oncogenic role of METTL3 and its downstream target oncogenes in CC cells. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to screen the target genes of METTL3. m6A level of mRNA was measured by an m6A-RNA methylation quantification kit. First, we investigated the expression of m6A regulator gene (METTL3) mRNA and proteins by qRT-PCR and western blot assays in cervical cancer cell lines. In addition, we performed a series of functional studies to investigate the oncogenic role of METTL3 and its downstream target oncogenes in CC cells. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-seq) was used to screen the target genes of METTL3. m6A level of mRNA was measured by an m6A-RNA methylation quantification kit. ResultsThe level of m6A RNA methylation was significantly increased in CC cells. METTL3 is a major catalytic enzyme involved in the abundant m6A RNA modification and plays an important role in carcinogenesis. We observed that METTL3 expression was frequently up-regulated in CC cell lines. Functional studies with METTL3 knockdown in CC cells dramatically inhibited cellular proliferation, migratory potential and colony formation abilities. Mechanistically, MeRIP-seq illustrated that Yin-Yang 1 (YY1) as a target of METTL3. Recent studies reported that YY1 is highly expressed in different types of cancer, whereby it is associated with cell proliferation, metastasis, survival, metabolic reprogramming, and poor patient survival. The TCGA data analysis revealed that YY1 mRNA and protein were highly expressed cervical cancer tissues. In addition, Pearson correlation analysis showed that highly expressed METTL3 was positively correlated with YY1 expression. Thus, the METTL3/m6A/YY1 axis promotes cervical carcinogenesis. The level of m6A RNA methylation was significantly increased in CC cells. METTL3 is a major catalytic enzyme involved in the abundant m6A RNA modification and plays an important role in carcinogenesis. We observed that METTL3 expression was frequently up-regulated in CC cell lines. Functional studies with METTL3 knockdown in CC cells dramatically inhibited cellular proliferation, migratory potential and colony formation abilities. Mechanistically, MeRIP-seq illustrated that Yin-Yang 1 (YY1) as a target of METTL3. Recent studies reported that YY1 is highly expressed in different types of cancer, whereby it is associated with cell proliferation, metastasis, survival, metabolic reprogramming, and poor patient survival. The TCGA data analysis revealed that YY1 mRNA and protein were highly expressed cervical cancer tissues. In addition, Pearson correlation analysis showed that highly expressed METTL3 was positively correlated with YY1 expression. Thus, the METTL3/m6A/YY1 axis promotes cervical carcinogenesis. ConclusionsTaken together, our findings demonstrated the oncogenic role of METTL3 in cervical cancer by regulating YY1 expression in an m6A-dependent manner and provide a new insight into the pathogenesis of CC. Hence, METTL3/m6A/YY1 axis represents a potential target for CC therapy. Taken together, our findings demonstrated the oncogenic role of METTL3 in cervical cancer by regulating YY1 expression in an m6A-dependent manner and provide a new insight into the pathogenesis of CC. Hence, METTL3/m6A/YY1 axis represents a potential target for CC therapy.