BACKGROUND & AIMS: RNA N 6-methyladenosine (m 6 A) modification has recently emerged as a new regulatory mechanism in cancer progression. We aimed to explore the role of the m 6 A regulatory enzyme METTL3 in colorectal cancer (CRC) pathogenesis and its potential as a therapeutic target. METHODS: The expression and clinical implication of METTL3 were investigated in multiple human CRC cohorts. The underlying mechanisms of METTL3 in CRC were investigated by integrative m 6 A sequencing, RNA sequencing, and ribosome profiling analyses. The efficacy of targeting METTL3 in CRC treatment was elucidated in CRC cell lines, patient-derived CRC organoids, and Mettl3-knockout mouse models. RESULTS: Using targeted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 dropout screening, we identified METTL3 as the top essential m 6 A regulatory enzyme in CRC. METTL3 was overexpressed in 62.2% (79/127) and 88.0% (44/50) of primary CRCs from 2 independent cohorts. High METTL3 expression predicted poor survival in patients with CRC (n ¼ 374, P < .01). Functionally, silencing METTL3 suppressed tumorigenesis in CRC cells, human-derived primary CRC organoids, and Mettl3-knockout mouse models. We discovered the novel functional m 6 A methyltransferase domain of METTL3 in CRC cells by domain-focused CRISPR screening and mutagenesis assays. Mechanistically, METTL3 directly induced the m 6 A-GLUT1-mTORC1 axis as identified by integrated m 6 A sequencing, RNA sequencing, ribosome sequencing,

ObjectivesTo identify the cooperation of authors, countries, institutions and explore the hot topics’ prospects regarding research of prostate diseases and erectile dysfunction (ED).MethodsPublications on research of prostate diseases and ED were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analyses were performed using VOSviewer and CiteSpace software. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords.ResultsA total of 2,599 articles related to study of prostate diseases and ED were identified. We observed gradually increasing in the number of publications from 1998 to 2016, and the trend was to be relatively stable in the past 3 years. Journal of Sexual Medicine (243 papers) owned the highest number of publications and Journal of Urology was the most co-cited journal. Mulhall John P (52 papers) was the top most productive authors and Mcvary Kebin T with the largest numbers of citations (1,589 co-citations) during the past decades. There were active collaborations among the top authors. The USA was the leading contributor in this field with 1,078 papers. Active cooperation between countries and between institutions was observed. The main hot topics included matters related to erectile dysfunction, prostate cancer, quality-of-life, radical prostatectomy, sexual function, and BPH.ConclusionBibliometric analysis provides a comprehensive overview of the development of scientific literature, allowing relevant authors and research teams to recognize the current research status in this field and at the same time provide a reference for formulating future research directions.

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