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Human Cell

, Volume 33, Issue 1, pp 140–147 | Cite as

CCND1 silencing suppresses liver cancer stem cell differentiation through inhibiting autophagy

  • Hongying ZhangEmail author
Research Article
  • 68 Downloads

Abstract

Liver cancer stem cells (LCSCs) are responsible for the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). This study aimed to explore the role of CCND1 (Cyclin D1), an oncogene in HCC, in regulating LCSC differentiation and to elucidate whether autophagy was involved in this process. The CCND1 mRNA level was examined by qRT-PCR. The protein levels of autophagy markers (Becin-1 and LC3II) were examined by western blot to evaluate autophagy level. CD133 was used as a LCSC marker and CD133 + cell percentage in HCC cells was detected by flow cytometry. Immunohistochemistry staining was performed to detect CD133 expression in SMMC-7721 cell-implanted tumor sections. The results showed that CCND1 expression was higher in HCC cell lines than that in normal hepatocyte L02 cells. Furthermore, CCND1 overexpression increased CD133 + cell percentage and protein levels of Becin-1 and LC3II in HepG2 and SMMC-7721 HCC cells. In contrast, CCND1 silencing exerted the opposite effect. Moreover, treatment with the autophagy activator rapamycin effectively abrogated the CCND1 silencing-reduced CD133 + cell percentage. Further in vivo assays demonstrated that CCND1 silencing decreased expression of CD133, Becin-1 and LC3II in xenograft tumors of SMMC-7721 cells. Taken together, CCND1 silencing suppresses LCSC differentiation through inhibiting autophagy.

Keywords

CCND1 Autophagy Liver cancer stem cell Hepatocellular carcinoma CD133 

Notes

Funding

This study was supported by grants from Natural Science Foundation of Jiangxi Province (Grant no. 20151BAB205100).

Compliance with ethical standards

Conflict of interest

The authors declared that there were no conflicts of interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study was approved by The Second Affiliated Hospital of Nanchang University (Nanchang, China).

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Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of GastroenterologyThe Second Affiliated Hospital of Nanchang UniversityNanchangChina

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