title: MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression.
abstract: MicroRNAs (miRNAs or miRs) have been found to participate in the development and malignant progression of human cancers by negatively mediating the expression of their target genes. Recently, miR‑33b has been reported to be involved in multiple types of human cancer, including hepatocellular carcinoma (HCC). However, the underlying regulatory mechanisms of miR‑33b in HCC cell growth and metastasis remain largely unclear. In the present study, RT-qPCR revealed that miR‑33b was significantly downregulated in HCC tissues compared to their matched adjacent normal tissues. Moreover, the miR‑33b level was significantly lower in advanced-stage HCC (stages T3-T4) compared to early-stage HCC (stages T1-T2). Furthermore, it was also downregulated in the HCC cell lines, LH86, HepG2, LMH and PLHC-1, when compared with the THLE-3 normal human liver cells. We further demonstrated that the overexpression of miR‑33b led to a significant decrease in the proliferation, migration and invasion of HepG2 and LH86 cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR‑33b, and its protein expression was negatively regulated by miR‑33b in HepG2 and LH86 cells. Moreover, the restoration of SALL4 expression markedly reversed the inhibitory effect of miR‑33b overexpression on the proliferation, migration and invasion of HepG2 and LH86 cells, indicating that SALL4 is involved in miR‑33b-mediated malignant phenotypes of HCC cells. Furthermore, we found that SALL4 was significantly upregulated in HCC tissues compared to their matched adjacent normal tissues, and its increased expression was significantly associated with the advanced malignancy of HCC. Moreover, SALL4 was also upregulated in HCC cell lines compared to the THLE-3 normal human liver cells. Finally, we found that the SALL4 expression inversely correlated with the miR‑33b level in HCC tissues. On the whole, the findings of our study demonstrate that miR‑33b suppresses the proliferation and metastasis of HCC cells through the inhibition of SALL4 expression. Therefore, miR‑33b/SALL4 may become a potential therapeutic target for the treatment of HCC.
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, The Third Clinical Medical School of Inner Mongolia Medical University (Baogang Hospital of Inner Mongolia), Baotou, Inner Mongolia 014010, P.R. China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Jingling
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Tuankui
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of General Surgery, The 4th Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Furong
authors.initials: F
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Baotou Eighth Hospital, Baotou, Inner Mongolia 014040, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D012984:Software; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C550416:MIRN33a microRNA, human; D035683:MicroRNAs; C472575:SALL4 protein, human; D014157:Transcription Factors