title: BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells.
abstract: Bcl-2-associated transcription factor 1 (BCLAF1) is known to be involved in multiple biological processes. Although several splice variants of BCLAF1 have been identified, little is known about how BCLAF1 splicing is regulated or the contribution of alternative splicing to its developmental functions. Here we find that inclusion of alternative exon5a was significantly increased in colorectal cancer (CRC) samples. Knockdown of the BCLAF1 protein isoform resulting from exon5a inclusion inhibited growth and that its overexpression increased tumorigenic potential. We also found that the splicing factor SRSF10 stimulates inclusion of exon5a and has growth-inducing activity. Importantly, the upregulation of SRSF10 expression observed in clinical CRC samples parallels the increased inclusion of BCLAF1 exon5a, both of which are associated with higher tumour grade. These findings identify SRSF10 as a key regulator of BCLAF1 pre-mRNA splicing and the maintenance of oncogenic features in human colon cancer cells.
authors.affiliation: Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Xuexia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1] Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China [2].
authors.forename: Xuebing
authors.initials: X
authors.lastname: Li
authors.affiliation: Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Wenwu
authors.initials: W
authors.lastname: Wu
authors.affiliation: Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Surgery, Zhongshan Hospital, Fudan University School of Medicine, Shanghai 200031, China.
authors.forename: Qiulei
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Department of Surgery, Zhongshan Hospital, Fudan University School of Medicine, Shanghai 200031, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Surgery, Zhongshan Hospital, Fudan University School of Medicine, Shanghai 200031, China.
authors.forename: Guohao
authors.initials: G
authors.lastname: Wu
authors.affiliation: 1] Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China [2] Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: 1] Key laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China [2] Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D012322:RNA Precursors / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C119386:BCLAF1 protein, human; C539097:Bclaf1 protein, mouse; D018797:Cell Cycle Proteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C115188:SRSF10 protein, human; C000599974:SRSF10 protein, mouse; D025521:Tumor Suppressor Proteins; D000068103:Serine-Arginine Splicing Factors