Background: Coiled-coil domain-containing protein 34 (CCDC34), which belongs to the CCDCs family, has been recently reported to be up-regulated in various kinds of tumors. However, its role in the development of hepatocellular carcinoma (HCC) still remains unclear.
Materials and methods: In this study, real-time polymerase chain reaction (RT-PCR) and Western blot analysis were performed to measure the mRNA and protein levels of CCDC34 in clinical samples. Kaplan-Meier method was used to analyze the relationship between CCDC34 and the prognosis in HCC patients. CCK-8 and colony formation assays were conducted to investigate CCDC34's effect on the cell proliferation, and Transwell assays were used to detect CCDC34's effect on the cell metastasis. Moreover, subcutaneous xenograft tumor model and lung metastasis model were applied to confirm the impact of CCDC34 on the HCC development. Lastly, RNA sequencing and Western blot analysis were performed to probe the underlying mechanism of CCDC34's effect on HCC.
Results: CCDC34 was significantly induced in HCC tissues, and the overexpression of CCDC34 predicted the poor outcomes among HCC patients. It was verified by the in vitro and in vivo experiments that CCDC34-knockdown potently inhibited the proliferation and metastasis of HCC cells. Subsequent results indicated that CCDC34 inhibition can affect the activation of protein kinase B (PKB or AKT) as well as epithelial-mesenchymal transition (EMT) process.
Conclusion: CCDC34 is significantly associated with HCC. It will become a promising prognostic biomarker and therapeutic target against HCC.
Keywords: CCDC34; CCND1; EMT; HCC; PI3K/AKT; proliferation.
© 2020 Lin et al.
Conflict of interest statement
The authors report no conflicts of interest in this work.
CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation, apoptosis and migration.Oncotarget. 2015 Sep 22;6(28):25856-67. doi: 10.18632/oncotarget.4624. Oncotarget. 2015. PMID: 26312564 Free PMC article.
Overexpression of Coiled-Coil Domain-Containing Protein 34 (CCDC34) and its Correlation with Angiogenesis in Esophageal Squamous Cell Carcinoma.Med Sci Monit. 2018 Feb 3;24:698-705. doi: 10.12659/msm.908335. Med Sci Monit. 2018. PMID: 29397026 Free PMC article.
MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1.Yonsei Med J. 2019 Mar;60(3):267-276. doi: 10.3349/ymj.2019.60.3.267. Yonsei Med J. 2019. PMID: 30799589 Free PMC article.
FoxM1 overexpression promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma.World J Gastroenterol. 2015 Jan 7;21(1):196-213. doi: 10.3748/wjg.v21.i1.196. World J Gastroenterol. 2015. PMID: 25574092 Free PMC article.
MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway.Mol Cancer. 2017 Jun 12;16(1):103. doi: 10.1186/s12943-017-0675-y. Mol Cancer. 2017. PMID: 28606154 Free PMC article.