Identification of Genes and MicroRNAs Involved in Ovarian Carcinogenesis

Emerging evidence has suggested that glycolysis is enhanced in cancer-associated fibroblasts (CAF), and miR-186 is downregulated during the CAF formation. However, it is not clear whether miR-186 is involved in the regulation of glycolysis and what the role of miR-186 plays during the CAF formation. In this study, quantitative PCR analysises show miR-186 is downregulated during the CAF formation. Moreover, miR-186 targets the 3' UTR of Glut1, and its overexpression results in the degradation of Glut1 mRNA, which eventually reduces the level of Glut1 protein. On the other hand, knockdown of miR-186 increased the expression of Glut1. Both time course and dose response experiments also demonstrated that the protein and mRNA levels of Glut1 increase during CAF formation, according to Western blot and quantitative PCR analyses, respectively. Most importantly, besides the regulation on cell cycle progression, miR-186 regulates glucose uptake and lactate production which is mediated by Glut1. These observations suggest that miR-186 plays important roles in glycolysis regulation as well as cell cycle checkpoint activation.

Section: Discussionmentioning

confidence: 99%

miR-186 Regulates Glycolysis through Glut1 During the Formation of Cancer-associated Fibroblasts

Sun¹,

Hu²,

Xiong³

et al. 2014

“…Furthermore, Wan et al (2012) recently reported that most of the up-regulated genes were related to cell cycling. The cell cycle dissection is regulated by numerous molecular pathways and specific access points (Figure 2).…”

Section: Mirnas In Cell Cycle Regulationmentioning

confidence: 99%

MicroRNAs: Biogenesis, Roles for Carcinogenesis and as Potential Biomarkers for Cancer Diagnosis and Prognosis

Kavitha¹,

Vijayarathna²,

Jothy³

et al. 2014

MicroRNAs (miRNAs) are short non-coding RNAs of 20-24 nucleotides that play important roles in carcinogenesis. Accordingly, miRNAs control numerous cancer-relevant biological events such as cell proliferation, cell cycle control, metabolism and apoptosis. In this review, we summarize the current knowledge and concepts concerning the biogenesis of miRNAs, miRNA roles in cancer and their potential as biomarkers for cancer diagnosis and prognosis including the regulation of key cancer-related pathways, such as cell cycle control and miRNA dysregulation. Moreover, microRNA molecules are already receiving the attention of world researchers as therapeutic targets and agents. Therefore, in-depth knowledge of microRNAs has the potential not only to identify their roles in cancer, but also to exploit them as potential biomarkers for cancer diagnosis and identify therapeutic targets for new drug discovery.

“…Functional studies performed in cancer ce ll lines or animal models of various cancers suggest that, miRNAs can function as tumor suppressors, oncogenes, and regulate cancer pathways (Farazi et al, 2011). Aberrant expression of specific miRNAs has been reported in many tumor types 1 such as CRC, breast cancer, cervical cancer, non-small cell lung cancer, ovarian cancer and bladder cancer as well as being associated with patients' survival data, metastasis, and other clinicopathological factors (Toyama et al, 2012;Wan et al, 2012;Shen et al, 2013;Wang et al, 2013;Xiao et al, 2013;Liu et al, 2014;Xu et al, 2014). A previous study showed that miR-32 expression was upregulated in CRC tissues, and high expression was significantly correlated with the tumor stage, distal metastases and poor prognoses (Wu et al, 2013b).…”

Section: Introductionmentioning

confidence: 99%

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Wu²,

Li³

et al. 2014

The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptasepolymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical followup information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.