Latexin exhibits tumor suppressor potential in hepatocellular carcinoma

Ni,Qing-Feng; Tian,Yuan; Kong,Liang-Liang; Lu,Ye-Ting; Ding,Wen-Zhou; Kong,Lian-Bao

doi:10.3892/or.2014.2966

Latexin exhibits tumor suppressor potential in hepatocellular carcinoma

Authors:
- Qing-Feng Ni
- Yuan Tian
- Liang-Liang Kong
- Ye-Ting Lu
- Wen-Zhou Ding
- Lian-Bao Kong
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Affiliations: The First Affiliated Hospital of Nanjing Medical University, The National Institute of Living Donor Liver Transplantation, Nanjing, Jiangsu 210029, P.R. China
Published online on: January 8, 2014 https://doi.org/10.3892/or.2014.2966
Pages: 1364-1372

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Abstract

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and latexin is downregulated in several types of human cancer. However, latexin expression in HCC remains unknown. mRNA expression of latexin in HCC samples and HCC-derived cell lines was detected by semi‑quantitative PCR and real-time PCR, while protein expression was assessed by immunohistochemistry. The role of latexin in the regulation of the proliferation of HCC-derived cells was investigated both in vitro and in vivo. Flow cytometry was used to differentiate cell cycle distribution in SK-hep-1 and YY-8103. In a total of 60 paired HCC specimens, compared with adjacent non-cancer tissues, latexin mRNA was downregulated in 42 specimens. Immunohistochemical analysis showed a significant reduction in latexin expression in HCC compared to control tissues. Overexpression of latexin inhibited SK-hep-1 and HepG2 cellular colony formation and tumor growth. Conversely, YY‑8103 and Focus cells transfected with shRNA enhanced colony formation and tumor growth. Latexin overexpression promoted cell cycle arrest in the G0/G1 phase in SK-hep-1 and silencing of latexin promoted the cell cycle transition from G0/G1 phase to S phase in YY-8103. The cyclin-dependent kinase inhibitors (CDKIs) (p21Cip1, p27Kip1, p15INK4B), cyclin D1 and cyclin E were shown to be differentially expressed in latexin-overexpressed cells and latexin-silenced cells. These results indicated that latexin may be an effective target for gene therapy.

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