通過microRNA-155下調(diào)SOCS-1在結(jié)直腸癌的表達(dá)促進(jìn)其轉(zhuǎn)移和侵襲
發(fā)布時(shí)間:2018-04-30 16:03
本文選題:結(jié)直腸癌 + miR-155。 參考:《川北醫(yī)學(xué)院》2015年碩士論文
【摘要】:目的:結(jié)直腸癌(CRC)具有生物學(xué)行為的復(fù)雜多變、容易復(fù)發(fā)轉(zhuǎn)移以及對(duì)化療藥物抵抗等特點(diǎn),導(dǎo)致病人的生存期縮短。因此,盡可能闡明結(jié)直腸癌發(fā)生進(jìn)展的機(jī)制,尋找早期、有效的診斷方法以及制定合理的治療策略一直是結(jié)直腸癌實(shí)驗(yàn)研究領(lǐng)域的重點(diǎn)。微小RNA(micro RNAs,mi RNAs)是一種在多種真核生物總表達(dá),大小約為18-25個(gè)核苷酸的非編碼的小分子RNA。目前研究認(rèn)為mi RNAs可以參與細(xì)胞發(fā)育、增殖、分化和凋亡等。已知人類基因組中確認(rèn)的mi RNA大約有500個(gè),其中約有200多種mi RNA序列與癌癥發(fā)生有關(guān)。micro RNA-155(mi R-155)定位于人類的染色體21q21,是由B細(xì)胞整合簇基因第3個(gè)外顯子高度保守的區(qū)域編碼。mi R-155是mi RNAs眾多中的一個(gè),許多研究者探索mi R-155與腫瘤的發(fā)生、發(fā)展之間的關(guān)系,因?yàn)樗赡軙?huì)成為腫瘤早期發(fā)現(xiàn)、早治療的新途徑。因此,此次實(shí)驗(yàn)是為了驗(yàn)證mi R-155在結(jié)直腸癌發(fā)生發(fā)展中的作用機(jī)制。方法:收集川北醫(yī)學(xué)院附屬醫(yī)院胃腸外科術(shù)前未經(jīng)任何治療的結(jié)直腸癌標(biāo)本76例及正常的直腸粘膜組織,應(yīng)用細(xì)胞培養(yǎng)、實(shí)時(shí)定量反向酶-PCR(q RT-PCR)、mi RNA的轉(zhuǎn)染、MTT分析法、遷移和侵襲試驗(yàn)和Western blot分析法,分析mi R-155在直腸癌的發(fā)生、發(fā)展中的作用及相關(guān)的臨床病理間的關(guān)系。結(jié)果:1.mi R-155在結(jié)直腸癌細(xì)胞中的表達(dá)水平比正常組織要高,兩者之間差異有統(tǒng)計(jì)學(xué)意義(P0.05),mi R-155的高表達(dá)與TNM分期,淋巴結(jié)及遠(yuǎn)處轉(zhuǎn)移明顯相關(guān)(P0.05)。然而,與其他臨床病理特征之間如年齡、性別、腫瘤大小、組織學(xué)類型、浸潤深度、腫瘤位置無顯著的相關(guān)性。2.mi R-155能夠調(diào)節(jié)CRC細(xì)胞遷移和侵襲,但沒有增殖的作用。3.mi R-155的高表達(dá)能夠使細(xì)胞與細(xì)胞之間的粘附和形態(tài)學(xué)發(fā)生了改變,從而有利于細(xì)胞遷移。4.mi R-155能夠調(diào)節(jié)降低socs-1在結(jié)直腸癌細(xì)胞的表達(dá)。結(jié)論:mi R-155的高表達(dá)在CRC的遷移和侵襲中起著重要作用。mi R-155的高表達(dá)夠使細(xì)胞與細(xì)胞之間的粘附和形態(tài)學(xué)發(fā)生了改變。mi R-155可能通過socs-1/ZEB-1/E-cadherin的軸對(duì)結(jié)直腸癌細(xì)胞的調(diào)控有關(guān)。這可能是結(jié)直腸癌轉(zhuǎn)移和侵襲相關(guān)機(jī)制的重要線索。
[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.
【學(xué)位授予單位】:川北醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類號(hào)】:R735.34
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