title: Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation.
abstract: Macrophage migration inhibitory factor (MIF), a proinflammatory and immunoregulatory chemokine, plays important roles in cancer-related biological processes. However, few studies have focused on the clinical relevance of MIF and cyclin D1 expression in hepatocellular carcinoma cells (HCCs). In this study, MIF and cyclin D1 expression levels in HCC tissues and cell lines were significantly upregulated compared with adjacent normal tissues or a normal liver cell line. In HCC specimens, MIF expression positively correlated with cyclin D1 expression. Additionally, MIF and cyclin D1 expression positively correlated with tumor size. MIF knockdown inhibited the proliferation of PLC and HepG2 cells and promoted apoptosis. However, small interfering RNA (siRNA) against MIF did not influence the cell cycle in these cells. In an in vivo xenograft model, MIF knockdown reduced the tumor growth rate. The expression levels of Bcl-2, p-caspase-3, BIM and Bax were upregulated, while the expression levels of cyclin D1, p-Akt and p-ERK were downregulated in MIF-knockdown cells. These findings indicate that MIF siRNA reduces proliferation and increases apoptosis in HCC cells. MIF knockdown inhibits the expression of growth-related proteins and induces the expression of apoptosis-related proteins, supporting a role for MIF as a novel therapeutic target for HCC.
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jian
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China. Department of General Surgery, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Wu
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China. Department of General Surgery, Guangzhou First Municipal People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D034741:RNA, Small Interfering; D019938:Cyclin D1