Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B.
Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B . Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC.
Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Minghua
M
Hu
Division of Cardiovascular Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, China.
Mingwei
M
Wang
Department of Anesthesiology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
Huihong
H
Lu
Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Xiaoming
X
Wang
Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Xiaoshan
X
Fang
Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Jinguo
J
Wang
Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Chenyang
C
Ma
Department of Oncology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, China.
Xiaobing
X
Chen
Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, 241001, China.
Hongping
H
Xia
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D042846:CDC2-CDC28 Kinases / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; C093090:CKS1B protein, human; C576996:MIRN1258 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin; D042846:CDC2-CDC28 Kinases
CKS1B; liver cancer; miR-1258; recurrence; stemness