title: MicroRNA-1908-5p contributes to the oncogenic function of the splicing factor SRSF3.
abstract: Serine/arginine (SR)-rich proteins that contain RS domains and SR repeats have diverse cellular functions including transcription, polyadenylation, translation, and RNA export. The splicing factor SRSF3, also termed SRp20, is the smallest member of the SR protein family and is a known proto-oncogene. Although it is implicated in the malignant phenotypes of various cancer cells, the molecular mechanism underlying SRSF3-mediated cancer progression is still obscure. We investigated here the oncogenic functions of SRSF3 in osteosarcoma U2OS cells. Knockdown of SRSF3 inhibited proliferation, clonogenicity, and metastatic potential including migration and invasion. It also decreased the level of miR-1908 independent of its host gene FADS1. Although FADS1 was not associated with SRSF3-mediated malignant properties, overexpression of miR-1908-5p increased cell proliferation, migration, and invasion, suggesting that miR-1908-5p is responsible for the oncogenic functions of SRSF3. Knockdown of SRSF3 decreased the expression of miR-1908-5p by inhibiting transactivation of NF-κB. We observed that miR-1908-5p downregulated NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB pathway by directly binding to the 3'UTR of NKIRAS2 mRNA. Consistent with overexpression of miR-1908-5p, knockdown of NKIRAS2 diminished the expression level of IκB-β and provoked translocation of NF-κB into the nucleus where it transcriptionally activates its target genes including miR-1908-5p expression, thus elevating the proliferation and metastatic potential. Taken together, our results demonstrate that SRSF3 confers the malignant characteristics on cancer cells via the SRSF3/miR-1908-5p/NKIRAS2 axis.
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Hye Ree
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Shin
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Hong
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.affiliation: Department of Cellular and Molecular Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.
authors.forename: Takbum
authors.initials: T
authors.lastname: Ohn
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.|Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Hyeon Ho
authors.initials: HH
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D000090943:Delta-5 Fatty Acid Desaturase; C000715470:MAS1 protein, human; C577645:MIRN1908 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; C491388:SRSF3 protein, human; D000068103:Serine-Arginine Splicing Factors; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: FADS1; NF-κB; NKIRAS2; SRSF3; miR-1908-5p