A long non-coding RNA named HOTTIP (HOXA transcript at the distal tip) coordinates the activation of various 5' HOXA genes which encode master regulators of development through targeting the WDR5/MLL complex. HOTTIP acts as an oncogene in several types of cancers, whereas its biological function in gastric cancer has never been studied. In the present study, we investigated the role of HOTTIP in gastric cancer. We found that HOTTIP was upregulated in gastric cancer cell lines. Knockdown of HOTTIP in gastric cancer cells inhibited cell proliferation, migration and invasion. Moreover, downregulation of HOTTIP led to decreased expression of homeobox protein Hox-A13 (HOXA13) in gastric cancer cell lines. HOXA13 was involved in HOTTIP‑induced malignant phenotypes of gastric cancer cells. Our data showed that the levels of HOTTIP and HOXA13 were both markedly upregulated in gastric cancer tissues compared with their counterparts in non-tumorous tissues. Furthermore, the expression levels of HOTTIP and HOXA13 were both higher in gastric cancer which was poorly differentiated, at advanced TNM stages and exhibited lymph node-metastasis. Spearman analyses indicated that HOTTIP and HOXA13 had a highly positive correlation both in non-tumor mucosae and cancer lesions. Collectively, these findings suggest that HOTTIP and HOXA13 play important roles in gastric cancer progression and provide a new insight into therapeutic treatment for the disease.
MicroRNAs have been documented playing key roles in cancer development and progression. Here, we investigate the role of miR-125b in gastric cancer metastasis. We found that the expression of miR-125b was up-regulated in gastric cancer tissue specimens compared with their corresponding nontumorous tissues, and the up-regulated miR-125b level was significantly associated with TNM stage and lymph node-metastasis. Overexpression of miR-125b promoted gastric cancer cell migration and invasion in vitro and metastasis in vivo. STARD13 and NEU1 were identified as direct target genes of miR-125b by luciferase assays, and they were involved in the cell migration and invasion regulated by miR-125b in gastric cancer. Taken together, miR-125b functions as an oncogene in gastric cancer and represents a new potential therapeutic target for gastric cancer.
Background. Clopidogrel inhibits the ADP receptor P2Y12 to keep down the platelet aggregation. The goal of our study is to investigate the contribution of P2Y12 promoter DNA methylation to the risk of clopidogrel resistance (CR). Methods. The platelet functions were measured by the VerifyNow P2Y12 assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides on P2Y12 promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association among P2Y12 DNA methylation, various biochemical characteristics, and CR. Result. Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1, P = 0.009; CpG2, P = 0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients (P = 0.026) and in subgroup of Albumin < 35 (P = 0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR. Conclusions. The evidence from our study indicates that P2Y12 methylation may bring new hints to elaborate the pathogenesis of CR.
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