Abstract. microRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. They have been increasingly shown to have aberrant expression in a number of tumor types. miR-192, -194 and -215 have not been comprehensively investigated using a large number of cases in colorectal cancer (CRC). We extracted total RNA from 107 CRC tissues and three CRC cell lines. Following polyadenylation and reverse transcription, the expression levels of miR-192, -194 and -215 were determined for evaluation of the association between expression levels and clinicopathological characteristics by a quantitative real-time polymerase chain reaction (real-time PCR) method. Finally, we studied the impact of miR-194 on cell proliferation in HCT-116 cells by MTT assay. miR-192, -194 and -215 were significantly downregulated in CRC tissues (all p<0.001, paired t-test) and cancer cell lines (all p<0.05) compared to non-tumor counterparts. Moreover, the expression levels of miR-192, -194 and -215 were demonstrated to be associated with increased tumor sizes (p=0.027, p=0.018, and p=0.027, respectively; Mann-Whitney U test). Also, there were marked correlations among these miRNAs in CRC tissues (all p<0.001, Pearson's regression analysis). Furthermore, we found that the overexpression of miR-194 could significantly inhibit cell proliferation in may be important biological markers as tumor suppressors in the carcinogenesis of CRC.

miR-203 may be related to the proliferation and invasion of gastric and colorectal cancers.

These findings imply that miR-194 might play an important role in gastric cancer invasion and progression.

Abstract. microRNAs (miRs) are endogenous small noncoding RNAs that are aberrantly expressed in various carcinomas. miR-152 and miR-148a have not been comprehensively investigated in ovarian cancer. Thus, the aim of this study was to identify the role of miR-152 and miR-148a in epithelial ovarian cancer. Total RNA was extracted from tissues of 78 patients with epithelial ovarian cancer, 17 normal ovarian epithelium tissues and two ovarian cancer cell lines. Using quantitative real-time PCR (qRT-PCR) followed by the 2 -ΔΔCT method for calculating the results, we found that the expression levels of miR-152 were significantly decreased in ovarian cancer tissues compared to normal ovarian epithelium tissues (p<0.05). However, although the expression of miR148a was also decreased in 65% of patients, no statistically significant difference in expression was found. A strong correlation was found between the expression of miR-152 and miR-148a (p<0.001, Pearson's correlation). The relationship between miR-152 or miR-148a expression levels in ovarian cancer and clinicopathological features, response to therapy and short-term survival was analyzed and the results showed that no correlation existed. In addition, we found that both miR-152 and miR-148a were down-regulated in ovarian cancer cell lines. After miR-152 or miR-148a mimics were transfected into ovarian cancer cell lines, the MTT cell proliferation assay showed that cell proliferation was significantly inhibited. Taken together, miR-152 and miR-148a may be involved in the carcinogenesis of ovarian cancer through deregulation of cell proliferation. They may be novel biomarkers for early detection or therapeutic targets of ovarian cancer. IntroductionOvarian cancer is one of the most common causes of death from gynecological malignancies. In addition, with an incidence of ~15,000 deaths annually, it is the fifth leading cause of cancer-related deaths among women in the United States (1). More than 90% of ovarian cancers are epithelial ovarian cancers (EOCs), which are derived from the ovarian surface epithelium (2). Due to a lack of effective biomarkers, ineffective tools for ovarian cancer screening, and non-specific symptoms in its early stages, more than two-thirds of patients with ovarian cancer are not diagnosed until the disease is in an advanced stage (3). Despite advances in early detection and the current standard treatment for advanced ovarian cancer, the 5-year survival rate is only 20-25% (4,5), which makes the development of alternative approaches urgent. Understanding the molecular alterations of ovarian cancer will help identify novel diagnostic markers or therapeutic targets, thereby improving the survival rates in this population of cancer patients.microRNAs (miRNAs or miRs) are a class of highly conserved, non-coding RNAs, approximately 19-25 nucleotides in length. They function as post-transcriptional regulators by binding to the 3'UTR regions of protein-encoding genes, which results in translational repression and gene silencing (6,7). Almost 30% ...

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MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. miR-192 and -215, which have the same "seed region", have not been comprehensively investigated using a large number of cases in gastric cancer. The total RNA was extracted from 118 gastric cancer tissues and three gastric cancer cell lines as well as matched non-tumor adjacent tissues (NATs). After polyadenylation and reverse transcription, expression levels of miR-192 and -215 were determined by real-time PCR and calculation using the 2(-∆∆CT) method for evaluation of the association between miR-192, and -215 expression levels and clinicopathological characteristics. There were no significant differences in miR-192 and -215 expression levels between gastric cancer tissues and non-tumor counterparts (both p > 0.05, paired t-test). Interestingly, miR-192 and -215 were down-regulated in MGC-803 cells, BGC-823 cells and SGC-7901 cells (all p < 0.01, paired t-test). Also, the down-regulation of miR-192 and -215 was demonstrated to be associated with increased tumor sizes (both p = 0.003, Mann-Whitney U test) and advanced Borrmann type tumors (p = 0.015 and p = 0.044, respectively, Kruskal-Wallis H test). Moreover, the expression of miR-192 was significantly lower in the pT4 stage of gastric cancer than in pT1, pT2 and pT3 stages (p = 0.026). Furthermore, there was a strong correlation between miR-192 and -215 in gastric cancer tissues (p < 0.001, Pearson regressions). miR-192 and -215 might be related to the proliferation and invasion of gastric cancer. Potentially, they could become important biomarkers.

Summary Glucosylceramide (GluCer) was accumulated in sphingomyelin synthase 1 (SMS1) but not SMS2 deficient mouse tissues. In current study, we studied GluCer accumulation-mediated metabolic consequences. Livers from liver-specific Sms1 /global Sms2 double-knockout (dKO) exhibited severe steatosis under a high-fat diet. Moreover, chow diet-fed ≥6-month-old dKO mice had liver impairment, inflammation, and fibrosis, compared with wild type and Sms2 KO mice. RNA sequencing showed 3- to 12-fold increases in various genes which are involved in lipogenesis, inflammation, and fibrosis. Further, we found that direct GluCer treatment ( in vitro and in vivo ) promoted hepatocyte to secrete more activated TGFβ1, which stimulated more collagen 1α1 production in hepatic stellate cells. Additionally, GluCer promoted more β-catenin translocation into the nucleus, thus promoting tumorigenesis. Importantly, human NASH patients had higher liver GluCer synthase and higher plasma GluCer. These findings implicated that GluCer accumulation is one of triggers promoting the development of NAFLD into NASH, then, fibrosis, and tumorigenesis.

Abstract. MicroRNAs are small, non-coding RNAs of endogenous origin. They have been increasingly shown to have altered expressions in many cancer types. The expression levels of miR-375 have not been comprehensively investigated in colorectal cancer. In this study, total RNA was extracted from 95 pairs of colorectal cancer tissues and non-tumor adjacent tissues, as well as from three colorectal cancer cell lines (HT-29, HCT-116 and SW-620). After polyadenylation and reverse transcription, we determined the expression levels of miR-375 by real-time PCR and calculated the difference in expression using the 2 -∆∆Ct method. We assessed the correlation between the expression levels of miR-375 and clini copathological characteristics of colorectal cancer. miR-375 expression was frequently downregulated in the colorectal cancer tissues compared to the non-tumor counterparts (p<0.001; paired t-test). Moreover, a significantly low expression of miR-375 was also found in the colorectal cancer cell lines (HT-29, p=0.002; HCT-116, p<0.001; SW-620, p=0.004; paired t-test). However, there were no significant correlations between the low expression of miR-375 and tumor size, histological grade, pT stage, pN stage and pTNM stage (all P>0.05, non-parametric test; Mann-Whitney U test between two groups and Kruskal-Wallis H test for three or more groups). miR-375 may be involved in the carcinogenesis of colorectal cancers and may be a potential biomarker for colorectal cancers.