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The Expression Of MicroRNA-141 In Colorectal Cancer And The Target Gene Prediction

Posted on:2017-09-06Degree:MasterType:Thesis
Country:ChinaCandidate:H Q MaFull Text:PDF
GTID:2334330485473946Subject:Surgery
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Objective:In recent years, colorectal cancer has become one of the most common malignant digestive tract cancers. In the past 30 years, the incidence of colorectal cancer has increased significantly, which has become the fourth cause of death in patients with malignant tumor. At the same time, the lifetime and quality of patientshas been seriously threatened. Early screening of colorectal cancer for urban patients in China has been gradually carried out, while in the vast areas of China it is not widespread. In most cases locally advanced colorectal cancer and metastasis have happened. So surgical excision is not efficient, thus leading to the loss of operation chances.For the advanced colorectal cancer, postoperative recurrence rate is high with a poor prognosis. According to the studies of the pathogenesis of colorectal cancer at gene and molecular levels, the molecular markers have been investigated for the early diagnosis of colorectal cancer, and the new methods of treatment were explored. MicroRNAs(miRNA) are non-coding small molecules which are composed of 18-25 nucleotides. As single stranded RNA molecules, their mainfunction is to target the gene 3 ' untranslated region(UTR), thus causing target mRNA degradation or translational repression. Furthermore, they could regulate the expression of endogenous genes and cell activities. In recent years, many studies have found that miRNA plays an important role in many cancer occurrence, development and prognosis. Among them, miRNA-200 family has made great contribution to suppressing the carcinogenesis. As an important member of the miRNA-200 family, miR-141 plays as tumor suppressor genes or oncogenes which may be associated with tumor cell differentiation, proliferation, invasion, migration and metastasis. This study intends to detect the expression of miR-141 in 26 cases of colorectal cancer tissues and paired normal tissues using quantitative real-time PCR assay. Furthermore, target genes bound by miR-141 was predicted by the bioinformatics analysis. The function of the target genes were analyzed by GO analysis, and the mechanism of the colorectal cancer occurrence and development were further explored.Method:1 Twenty-six cases of surgical colorectal cancer tissues and their corresponding adjacent normal colorectal tissues were obtained from the second department of Surgery Fourth Affiliated Hospital of Hebei Medical University during April 11, 2004 and March 1, 2015. Real-time quantitative PCR assays were performed to detect the expression of miR-141 in 26 colorectal carcinoma and adjacent normal tissues, and the clinical and pathological classifications such as age, gender, invasive depth(T stage),lymph node metastasis(N stage), TNM stage, histologic, preoperative CEA level have also been investigated.3 Statistical analysis:The SPSS 13.00 software was used. The expression of miR-141 in the test group and the control group has been analized by two tailed Student's t-tests. The differences of the clinical and pathological features of colorectal were analyzed by one-way analysis of variance. All data represent meanąSD of three independent experiments. P<0.05 was considered statistically significant.4 By bioinformatics analysis, target genes of miR-141 were pridicted. Then the function of these target genes were screened by GO analysis. The correlated functions containes signal transduction of cell apoptosis, vesicle docking, membrane docking and ectodermal dysplasia.Results:1 The relative expression level of miR-141 was low in colorectal cancer tissues, compaired to normal tissues.?Ct value of colorectal cancer tissues was 11.686ą4.296,while the data of adjacent normal tissue was 13.321+3.827, the difference was statistically significant(P<0.05).2 The expression of miR-141 was not significsntly relavant to pathological and clinical parameters of age, gender, tumor in intestinal invasion depth(T stage), tumor with lymph metastasis situation(N stage) and TNM stage, histologic and CEA situation. In 18 cases of moderately differentiated adenocarcinoma and 8 cases of poorly differentiated adenocarcinoma the expression of microRNA-141 was 8.015(2.078-13.952) and 1.363(0.461-2.265),(P<0.05). The results indicated that the expression of miR-141 could probably be used as a prognostic indicator for colorectal cancer.3 Seventy-seven target genes weredetected by the bioinformatics analysis. Based on Gene Ontology databases, GO analysis of the target genes noted some target genes involved in apoptotic signaling pathway, vesicle docking, membrane docking and ectodermal development.Conclusions:1 The low expression of miR-141 suggested that it could probably play a role in colorectal cancer as a tumor suppressor gene.2 The expression of miR-141 was related to the histologic. The results suggested that the expression level of miR-141 was promised to be one of the prognostic indicators in colorectal cancer, thus participating in the judgement of the prognosis.3 By the bioinformatics analysis, target genes of miR-141 which were involved in cell apoptosis, vesicle docking, membrane docking and ectodermal dysplasia were predicted. They can resulted in many biological characteristics of corectal carcinoma cells.
Keywords/Search Tags:MicroRNA-141, Colorectal cancer, Histologic, Tumor suppressor gene, Target gen
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