Lee Jung Won, Kim Nayoung, Park Ji Hyun, Kim Hee Jin, Chang Hyun, Kim Jung Min, Kim Jin-Wook, Lee Dong Ho
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine, Samsung Changwon Hospital, Changwon, Korea.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
J Cancer Prev. 2017 Mar;22(1):33-39. doi: 10.15430/JCP.2017.22.1.33. Epub 2017 Mar 30.
MicroRNAs (miRNAs) are key post-translational mechanisms which can regulate gene expression in gastric carcinogenesis. To identify miRNAs responsible for gastric carcinogenesis, we compared expression levels of miRNAs between gastric cancer tissue and non-cancerous gastric mucosa according to status.
Total RNA was extracted from the cancerous regions of formalin-fixed, paraffin-embedded tissues of -positive (n = 8) or -negative (n = 8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays for biopsy samples from 107 patients consisted of control and gastric cancer with or without . And then, expression levels of miRNAs were compared according to subgroups.
A total of 156 miRNAs in the aberrant miRNA profiles across the miRNA microarray showed differential expression (at least a 2-fold change, < 0.05) in cancer tissue, compared to noncancerous mucosa in both of -negative and -positive samples. After 10 promising miRNAs were selected, validations by TaqMan miRNA assays confirmed that two miRNAs (hsa-miR-135b-5p and hsa-miR-196a-5p) were significantly increased and one miRNA (hsa-miR-145-5p) decreased in cancer tissue compared to non-cancerous gastric mucosa at -negative group. For -positive group, three miRNAs (hsa-miR-18a-5p, hsa-miR-135b-5p, and hsa-miR-196a-5p) were increased in cancer tissue. hsa-miR-135b-5p and hsa-miR-196a-5p were increased in gastric cancer in both of -negative and -positive.
miRNA expression of the gastric cancer implies that different but partially common gastric cancer carcinogenic mechanisms might exist according to status.
微小RNA(miRNA)是关键的翻译后调控机制,可在胃癌发生过程中调节基因表达。为了鉴定与胃癌发生相关的miRNA,我们根据状态比较了胃癌组织与非癌性胃黏膜中miRNA的表达水平。
从福尔马林固定、石蜡包埋的肠型胃癌-阳性(n = 8)或-阴性(n = 8)患者的癌组织区域提取总RNA。基于桑格miRBase使用3523个miRNA谱微阵列分析RNA表达。对来自107例患者(包括对照组以及有或无的胃癌患者)的活检样本,使用TaqMan miRNA检测进行验证分析。然后,根据亚组比较miRNA的表达水平。
与非癌性黏膜相比,miRNA微阵列上异常miRNA谱中的总共156个miRNA在癌组织中显示出差异表达(至少2倍变化,<0.05),在-阴性和-阳性样本中均如此。在选择了10个有前景的miRNA后,通过TaqMan miRNA检测进行的验证证实,与-阴性组的非癌性胃黏膜相比,癌组织中有两个miRNA(hsa-miR-135b-5p和hsa-miR-196a-5p)显著增加,一个miRNA(hsa-miR-145-5p)减少。对于-阳性组,癌组织中有三个miRNA(hsa-miR-18a-5p、hsa-miR-135b-5p和hsa-miR-196a-5p)增加。hsa-miR-135b-5p和hsa-miR-196a-5p在-阴性和-阳性的胃癌中均增加。
胃癌的miRNA表达表明,根据状态可能存在不同但部分共同的胃癌致癌机制。