Latexin exhibits tumor suppressor potential in hepatocellular carcinoma

Abstract

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.

Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice

“…We and others have shown that Lxn is downregulated in leukemia, lymphoma, and several other cancers (Li et al., 2011, Liu et al., 2012, Mitsunaga et al., 2012, Abd Elmageed et al., 2013, Muthusamy et al., 2013, Ni et al., 2014). Since young Lxn −/− mice did not show any obvious sign of hematological malignancy, we asked whether aging could promote tumor development in Lxn −/− mice.…”

Latexin sensitizes leukemogenic cells to gamma-irradiation-induced cell-cycle arrest and cell death through Rps3 pathway

“… 3 It is downregulated in several types of solid and liquid tumors, and overexpression of Lxn inhibits tumor cell growth. 4 , 5 , 6 , 7 , 8 In lymphoma, the tumor suppressor function of Lxn is mediated through Bcl-2-induced apoptosis. 5 Moreover, Lxn was reported to be a TNF-responsive gene in human papillovirus-infected keratinocytes, suggesting that it may contribute to TNF-induced suppression of cervical cancer.…”

Bone Microenvironment Changes in Latexin Expression Promote Chemoresistance

“…LXN has homology to two other proteins/genes, tazarotene-induced gene 1 (TIG1) and cystatin C, both of which have been reported to be tumor suppressors (36,37). LXN expression has been suggested to be a tumor suppressor itself as it has been shown to inhibit tumor cell growth in gastric cancer (14), leukemia (15), melanoma (16), PCa (38), hepatocellular carcinoma (39) and breast cancer (40). In addition to being a potential tumor suppressor, LXN negatively regulates hematopoietic stem cell self-renewal in mice, resulting in an inverse relationship between LXN expression and HSC population size (17,18,41).…”