title: Retinoic acid induced 16 enhances tumorigenesis and serves as a novel tumor marker for hepatocellular carcinoma.
abstract: Our previous work identified downregulated miR-483-5p in hepatocellular carcinoma (HCC). This study aims to identify the target of miR-483-5p, evaluate the potential value of this target as a tumor marker for HCC and explore the role of this target in HCC tumorigenesis. Upregulated retinoic acid induced 16 (RAI16) (17/18 cases) was negatively correlated with downregulated miR-483-5p (14/18 cases) in HCC tissues. The dual-luciferase reporter assay showed that RAI16 is a target of miR-483-5p. Immunohistochemistry analysis showed RAI16 was moderate or strong staining in tumor tissues but negative or weak staining in adjacent non-tumor tissues. The sensitivity and speciﬁcity of RAI16 for HCC diagnosis were 70.6 and 93.6%, respectively, and increased to 80.9 and 92.0% when combined with glypican-3. Finally, overexpression or knockdown of RAI16 increased or decreased cell viability and colony formation in HCC cell lines and enhanced or inhibited tumor cell growth in xenograft nude mice. Mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and transforming growth factor-β pathways were mostly affected by RAI16. RAI16 could activate the phosphorylation of ERK1/2 and SMAD2/3. In conclusion, RAI16 may serve as a useful therapeutic agent for HCC gene therapy and tumor marker for HCC diagnosis.
authors.affiliation: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Ruo-Yu
authors.initials: RY
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
authors.forename: Zhong-Tian
authors.initials: ZT
authors.lastname: Qi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors; D011506:Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D011506:Proteins; C547416:FHIP2B protein, human; C548912:MIRN483 microRNA, human