No abstract

No abstract

Aberrant microRNA (miRNA) expression is presently proposed to correlate with various human cancers and common single-nucleotide polymorphisms (SNP) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. However, whether miRNAs SNP alter gastric cancer susceptibility is still unclear. Here we investigated the possible role of a common A/G polymorphism (rs895819) within hsa-mir-27a in the development or progression of gastric cancer, and assessed the effect of rs895819 on the expression of miR-27a and its target gene Zinc finger and BTB domain containing 10 (ZBTB10). In the present case-control study, we found that subjects with the variant genotypes (AG + GG) showed a significantly increased risk of gastric cancer relative to AA carriers (adjusted odds ratio = 1.48, 95% confidence interval 1.06-2.05; P = 0.019). The elevated risk was especially evident in older subjects (age >58 years), men, nonsmokers and rural subjects. A significant association of hsamir-27a variant genotypes with lymph node metastasis was also observed. Further functional analyses indicated that variant genotypes might be responsible for elevated miR-27a levels and reduced ZBTB10 mRNA. Moreover, an inverse correlation was found between ZBTB10 and miR-27a levels. In conclusion, we were the first to show that a common polymorphism (rs895819) in hsa-mir-27a, by modulating miR-27a and ZBTB10 levels, acted as an important factor of the gastric cancer susceptibility. (Cancer Sci 2010; 101: 2241-2247 G astric cancer is one of the commonest malignant tumors in the world.(1) Of all the treatment modalities, only surgical resection may offer an opportunity for long-term survival. However, in most cases, curative resection of the tumor is impossible because of the advanced stage at the time of diagnosis.(2) In this regard, early detection of gastric cancer currently is the most important measure to decrease disease-associated mortality. Therefore, it appears very important to find novel diagnosis biomarkers to improve patient prognosis.MicroRNAs (miRNAs), a class of small endogenous noncoding RNA, negatively regulate post-transcriptional gene expression by directly cleaving target mRNA or by inhibiting their translation.(3) Although the underlying biological functions are not completely clear, it has been shown to play important roles in a variety of cellular processes including apoptosis, differentiation and cell proliferation.(4-6) Recent studies have identified that aberrant miRNAs expression correlated with various human cancers such as colon tumors, breast cancer, lung cancer, pancreatic cancer and gastric cancer. There is increasing evidence that single nucleotide polymorphisms (SNP) or mutations could make a significant contribution to disease susceptibility and outcome. The high degree of phylogenetic conservation in miRNA sequences determines that the functional variation in miRNAs may influence various biological processes. Therefore, a mutation or a SNP in miRNA genes might influence the transcrip...

Estrogen plays a critical role in breast cancer development and progression. However, the mechanism involved in the promotion of breast cancer development and progression by estrogen remains unclear although it has been intensively studied. In the present study, we investigated the estrogen inducibility and functional significance of H19 lncRNA in breast cancer cells and tumor tissues. The screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19 lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer cells than in ER-negative MDA-MB-231 cells. 17β-estradiol produced a dose- and time-dependent induction of H19 expression in MCF-7 cells, which was mediated via ERα as evident by the blockade of this 17β-estradiol effect with ICI 182780, a specific ER antagonist and knockdown of ERα using specific RNAi. Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen-induced cell growth while overexpression of H19 lncRNA stimulated cell proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER-negative tumor tissues. These results suggest that H19 is an estrogen-inducible gene and plays a key role in cell survival and in estrogen-induced cell proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker for breast cancer diagnosis and progression, and as a valuable target for breast cancer therapy.