title: Down-regulated PLAC8 promotes hepatocellular carcinoma cell proliferation by enhancing PI3K/Akt/GSK3β/Wnt/β-catenin signaling.
abstract: Hepatocellular carcinoma (HCC) is a common, prevalent malignancy. Its poor prognosis is mainly related to high rate of diagnosis in non-curable stages, in which patients are suitable for palliative treatment. Placenta-specific 8 (PLAC8), also known as Onzin, is a small, highly conserved, cysteine-rich protein. In current study, we found that PLAC8 is prominently decreased in HCC tissues compared with adjacent tissues and patients with low level of PLAC8 suffered a poor prognosis. In addition, cellular function assays demonstrate that down-regulated PLAC8 promotes cell viability, proliferation and tumor formation both in vitro and in vivo. Furthermore, we validate that down-regulated PLAC8 enhances the activity of PI3K/Akt/GSK3β and Wnt/β-catenin signaling to promote cell proliferation. Moreover, we proved that highly expressed miR-185-5p targets PLAC8 in HCC tissues. In conclusion, our findings enlarged our knowledge about the roles of PLAC8 in HCC progression and miR-185-5p/PLAC8/β-catenin axis might be a novel pathway for HCC treatment.
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, 250021, China; Department of General Surgery, Shandong Cancer Hospital and Institute, Jinan, 250117, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of General Surgery, Shandong Cancer Hospital and Institute, Jinan, 250117, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chai
authors.affiliation: Department of General Surgery, Shandong Cancer Hospital and Institute, Jinan, 250117, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Shandong Cancer Hospital and Institute, Jinan, 250117, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Guan
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, 250021, China. Electronic address: qiliu_sphsu@sina.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, 250021, China. Electronic address: jjdu_sphsu@sina.com.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Du
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C506004:PLAC8 protein, human; D011506:Proteins; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: HCC; PI3K/Akt signaling; PLAC8; Wnt/β-catenin signaling; miR-185-5p