通过microRNA-155下调SOCS-1在结直肠癌的表达促进其转移和侵袭

发布时间：2018-04-30 16:03

本文选题：结直肠癌 + miR-155　；参考：《川北医学院》2015年硕士论文

【摘要】：目的:结直肠癌(CRC)具有生物学行为的复杂多变、容易复发转移以及对化疗药物抵抗等特点,导致病人的生存期缩短。因此,尽可能阐明结直肠癌发生进展的机制,寻找早期、有效的诊断方法以及制定合理的治疗策略一直是结直肠癌实验研究领域的重点。微小RNA(micro RNAs,mi RNAs)是一种在多种真核生物总表达,大小约为18-25个核苷酸的非编码的小分子RNA。目前研究认为mi RNAs可以参与细胞发育、增殖、分化和凋亡等。已知人类基因组中确认的mi RNA大约有500个,其中约有200多种mi RNA序列与癌症发生有关。micro RNA-155(mi R-155)定位于人类的染色体21q21,是由B细胞整合簇基因第3个外显子高度保守的区域编码。mi R-155是mi RNAs众多中的一个,许多研究者探索mi R-155与肿瘤的发生、发展之间的关系,因为它可能会成为肿瘤早期发现、早治疗的新途径。因此,此次实验是为了验证mi R-155在结直肠癌发生发展中的作用机制。方法:收集川北医学院附属医院胃肠外科术前未经任何治疗的结直肠癌标本76例及正常的直肠粘膜组织,应用细胞培养、实时定量反向酶-PCR(q RT-PCR)、mi RNA的转染、MTT分析法、迁移和侵袭试验和Western blot分析法,分析mi R-155在直肠癌的发生、发展中的作用及相关的临床病理间的关系。结果:1.mi R-155在结直肠癌细胞中的表达水平比正常组织要高,两者之间差异有统计学意义(P0.05),mi R-155的高表达与TNM分期,淋巴结及远处转移明显相关(P0.05)。然而,与其他临床病理特征之间如年龄、性别、肿瘤大小、组织学类型、浸润深度、肿瘤位置无显著的相关性。2.mi R-155能够调节CRC细胞迁移和侵袭,但没有增殖的作用。3.mi R-155的高表达能够使细胞与细胞之间的粘附和形态学发生了改变,从而有利于细胞迁移。4.mi R-155能够调节降低socs-1在结直肠癌细胞的表达。结论:mi R-155的高表达在CRC的迁移和侵袭中起着重要作用。mi R-155的高表达够使细胞与细胞之间的粘附和形态学发生了改变。mi R-155可能通过socs-1/ZEB-1/E-cadherin的轴对结直肠癌细胞的调控有关。这可能是结直肠癌转移和侵袭相关机制的重要线索。
[Abstract]:Objective: CRC has the characteristics of complex biological behavior, easy recurrence and metastasis, and resistance to chemotherapy drugs. Therefore, to elucidate the mechanism of colorectal cancer as much as possible, to search for early and effective diagnostic methods and to formulate reasonable treatment strategies have always been the focus of experimental research on colorectal cancer. Small RNA(micro RNAsmi RNASS is a non-coding small molecule expressed in a variety of eukaryotes, about 18-25 nucleotides in size. It is believed that mi RNAs can participate in cell development, proliferation, differentiation and apoptosis. There are about 500 known mi RNA identified in the human genome. There are more than 200 kinds of mi RNA sequences related to carcinogenesis. Micro RNA-155(mi R-155) is located on human chromosome 21q21. It is one of the many genes of mi RNAs, which is highly conserved in exon 3 of B cell integration cluster gene. Many researchers have explored the relationship between mi R-155 and tumorigenesis and development, as it may be a new approach to early detection and early treatment of tumors. Therefore, the purpose of this study was to verify the role of mi R-155 in the development of colorectal cancer. Methods: 76 specimens of colorectal cancer and normal rectal mucosa were collected from gastrointestinal surgery of affiliated Hospital of North Sichuan Medical College before operation. Cell culture and real-time quantitative reverse enzyme PCRX Q RT-PCRN mi RNA transfection assay were used. Migration and invasion test and Western blot analysis were used to analyze the role of mi R-155 in the occurrence, development and clinicopathological relationship of rectal cancer. Results the expression level of R155 in colorectal cancer cells was significantly higher than that in normal tissues. There was a significant correlation between the high expression of R155 and TNM stage, lymph node and distant metastasis. However, there was no significant correlation with other clinicopathological features such as age, sex, tumor size, histological type, depth of invasion and tumor location. However, the high expression of .3.mi R-155 can change the adhesion and morphology of the cells, which is beneficial to the migration of cells. 4. MIR-155 can regulate and decrease the expression of socs-1 in colorectal cancer cells. Conclusion the overexpression of cell line 1: miR-155 may play an important role in the migration and invasion of CRC. The high expression of R155 can change the adhesion and morphology of cells to cells, which may be related to the regulation of colorectal cancer cells by the axis of socs-1/ZEB-1/E-cadherin. This may be an important clue to the mechanism of metastasis and invasion of colorectal cancer.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.34

【参考文献】