Expression of hiwi gene in human gastric cancer was associated with proliferation of cancer cells

Abstract

Stem cell genetics research may be critical to our understanding of carcinogenesis, as both stem cells and cancer cells possess the ability to self-renew. Recent discoveries have indicated that the piwi family of genes plays an essential role in stem cell selfrenewal in diverse organisms. The hiwi gene, the human homolog of the piwi family, participates in germ cell proliferation and its overexpression may cause the development of germ cell malignancy, but its expression and function in epithelial solid cancers have not been explored. In the present study, we investigated whether there was an association between hiwi expression and human gastric cancer and its potential mechanism. RT-PCR findings demonstrated that hiwi was expressed in different gastric cancer cell lines. To identify the HIWI protein in gastric cancer, we developed a specific monoclonal antibody against HIWI and immunohistochemistry was performed on various gastric tissues. We found that the expression ratio of hiwi in normal gastric tissues, atrophic gastritis, intestinal metaplasia and gastric cancers was 10% (5/50), 36% (18/50), 36% (18/50) and 76% (38/50), respectively, which was consistent with precancerous development. Notably, the expression pattern of hiwi in gastric cancer tissues was similar to that of Ki67, which was used as a marker of proliferation. Moreover, the suppression of hiwi by antisense or RNAi inhibited the growth of gastric cancer cells and induced cell cycle arrest in G 2 /M phase. These results suggest that hiwi may be involved in the development of gastric cancer and is a potential target for cancer therapy. ' 2005 Wiley-Liss, Inc.Key words: hiwi; expression; gastric cancer; proliferation Although there is a high incidence of gastric cancer in Asia and gastric cancer remains one of the leading causes of cancer-related death worldwide, 1 the molecular mechanisms underlying its development are poorly understood. Stem cell research will greatly expand our understanding of the mechanisms of carcinogenesis because the homeostatic mechanisms mediating stem cell proliferation are the same processes that become dysregulated in carcinogenesis.2,3 Therefore, the study of stem cell genes may be critical to furthering our understanding of carcinogenesis and to the development of novel strategies for preventing and managing cancer. 4 Because of this, there is a growing interest in studying the roles of genes, which were initially found to be involved in stem cell selfrenewal, in the development of cancer. 5-7The hiwi gene is a human member of the piwi family, which represents the first class of genes known to be required for stem cell self-renewal in diverse organisms.8 Recent discoveries have shown that hiwi may participate in germ cell proliferation and its overexpression may cause germ cell malignancy development. 9These findings raise the hypothesis that hiwi may be present in other types of stem cells and likewise may be involved in the development of cancers.The hiwi gene, located in 12q24.33, was originally isolated from a h...

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

“…Moreover, the overexpression pattern of hiwi in gastric cancer tissues was similar to that of Ki67, which was used as a marker of growth of cancer cells. and the suppression of hiwi inhibited the growth of gastric cancer cells and induced cell cycle arrest in G2/M phase (Liu et al, 2006). Whereas, hiwi knockdown inhibits the growth of lung cancer in nude mice (Liang et al, 2013).…”

“…The Piwi family represents the first class of genes known to be required for stem cell self-renewal in diverse organisms such as jellyfish, Caenorhabditis elegans, D. melanogaster, zebrafish, mouse and humans (Liu et al, 2006). Hiwi mRNA is present in human CD34 (+) haematopoietic progenitor cells, but not in more differentiated cell populations (Sharma et al, 2001).…”

“…In addition to its function in stem cell renewal, overexpression of Hiwi in male germline cells correlates with the occurrence of seminomas, a testicular germ cell tumours (Qiao et al, 2002). Recently, accumulating reports have revealed that abnormal hiwi expression is associated with poorer prognosis of human malignant tumors, such as human esophageal squamous cell carcinoma (He et al, 2009), human adenocarcinoma of the pancreas (Grochola et al, 2008), human gastric cancer (Liu et al, 2006), and colorectal cancer (Oh et al, 2012). The alterations in mRNA expression of hiwi can increase the risk of tumour-related death in male human adenocarcinoma of the pancreas patients (Grochola et al, 2008); The expression of hiwi in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome (He et al, 2009); And the high degree of hiwi expression was significantly correlated with the lower degree of differentiation, deep invasion and perineural invasion (Oh et al, 2012).…”

Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients

“…An approach for stem cell identification could be expression analysis of stem cellassociated genes. Therefore, in this study, we evaluated the expression of three genes; Hiwi, human telomerase reverse transcriptase (hTERT) and survivin, which had previously been shown to be overexpressed in both stem cells and cancer cells (Altieri, 2003;Ju and Rudolph, 2006;Liu et al, 2006;Taubert et al, 2007).…”

“…Expression of Hiwi has been described in different cancers including seminomas, gastric carcinomas and soft-tissue sarcoma (STS) (Qiao et al, 2002;Liu et al, 2006;Taubert et al, 2007). In addition, we have recently reported an association between altered expression of Hiwi mRNA and a poor prognosis for STS patients (Taubert et al, 2007).…”