MicroRNA-381靶向調(diào)控LRH-1對結(jié)腸癌細(xì)胞增殖和侵襲影響及機(jī)制的研究
發(fā)布時間：2019-05-24 03:15
【摘要】：結(jié)腸癌是一種常見的惡性腫瘤,是在內(nèi)、外因素作用下發(fā)生的多基因表達(dá)失調(diào)的一種個體化疾病,嚴(yán)重威脅著人類生命健康。雖然大量研究已經(jīng)證實(shí),飲食和遺傳因素等在結(jié)腸癌的發(fā)生和發(fā)展中起著重要作用,但結(jié)腸癌惡性轉(zhuǎn)化及腫瘤細(xì)胞增殖、侵襲的關(guān)鍵因素還有待進(jìn)一步研究確定。微小RNA(micro RNAs,mi RNA)是一類長度約19-22核苷酸的RNA,通過與靶基因m RNA的3’-UTR非編碼區(qū)互補(bǔ)匹配來調(diào)控基因轉(zhuǎn)錄后表達(dá)。這種相互作用導(dǎo)致翻譯阻遏,多數(shù)情況下降低m RNA的表達(dá)水平。研究表明,多種mi RNA在人腫瘤中表達(dá)下調(diào)或上調(diào),包括結(jié)腸癌,這為腫瘤發(fā)生提供了新的分子基礎(chǔ)。Tang等首先報(bào)道了mi R-381在神經(jīng)膠質(zhì)瘤細(xì)胞中的作用。結(jié)果表明,mi R-381可促進(jìn)神經(jīng)膠質(zhì)瘤細(xì)胞在體外和體內(nèi)的增殖,此作用與減弱抑制MEK/ERK和AKT信號有關(guān)。然而,Rothschild等發(fā)現(xiàn)mi R-381在肺腺癌中的表達(dá)顯著下調(diào),低mi R-381表達(dá)水平與預(yù)后不良相關(guān)。此外,mi R-381通過上調(diào)Cdc2的活性來增強(qiáng)5-FU在腎癌細(xì)胞中的化療敏感性。mi R-381表達(dá)的變化也與MDR1基因的表達(dá)和多種藥物耐藥性的發(fā)展呈負(fù)相關(guān)。這些結(jié)果表明,mi R-381在癌細(xì)胞中的作用因腫瘤的不同而不同,因此,有必要研究其在結(jié)腸癌中的的生物學(xué)功能,為深入理解結(jié)腸癌的發(fā)生和發(fā)展開辟新的研究路徑。目的:在本研究中,我們首先檢測mi R-381在結(jié)腸癌組織和癌旁組織中的表達(dá)及與臨床病理特征的關(guān)系,再進(jìn)一步探討mi R-381對結(jié)腸癌細(xì)胞生長、增殖和侵襲的影響,然后預(yù)測并驗(yàn)證mi R-381的靶基因,闡明mi R-381在結(jié)腸癌發(fā)生發(fā)展中的作用,為深入理解結(jié)腸癌發(fā)病的潛在分子機(jī)制和開發(fā)新的有效分子治療靶點(diǎn)提供實(shí)驗(yàn)依據(jù)。方法:通過RT-PCR方法,觀察mi R-381在不同臨床分期的結(jié)腸癌組織及相應(yīng)癌旁組織中的表達(dá)及與臨床病理特征的關(guān)系;通過應(yīng)用RNA干擾技術(shù)沉默mi R-381表達(dá),觀察其對結(jié)腸癌細(xì)胞株生長、增殖及侵襲的影響,以及體內(nèi)成瘤能力的影響;通過應(yīng)用mi RNA靶基因預(yù)測軟件Target Scan、mi Randa和mi RWalk分析mi R-381的潛在靶基因,發(fā)現(xiàn)mi R-381能夠靶向結(jié)合LRH-1 3’UTR的ACAUAUA序列,并通過雙熒光素酶報(bào)告基因分析系統(tǒng)驗(yàn)證mi R-381是否與之特異結(jié)合;再以人結(jié)腸癌細(xì)胞株SW480和HCT116為研究對象,應(yīng)用mi R-381沉默和mi R-381過表達(dá)技術(shù),觀察其對結(jié)腸癌細(xì)胞株LRH-1表達(dá)的影響,進(jìn)一步驗(yàn)證mi R-381的靶點(diǎn);通過應(yīng)用RNA干擾技術(shù)沉默LRH-1表達(dá),觀察其對mi R-381抑癌作用的影響。結(jié)果:本課題三部分的具體結(jié)果內(nèi)容如下:第一部分mi R-381在結(jié)腸癌組織和癌旁組織中的表達(dá)情況本部分實(shí)驗(yàn)主要利用熒光定量RT-PCR方法觀察mi R-381在臨床切除的結(jié)腸癌標(biāo)本和癌旁組織中的表達(dá)情況。結(jié)果如下:1 mi R-381在結(jié)腸癌組織中表達(dá)情況RT-PCR結(jié)果表明mi R-381在結(jié)腸癌組織中的相對表達(dá)水平(0.50±0.08)顯著下調(diào),是癌旁組織(1.00±0.13)的0.5倍,兩者差異具有統(tǒng)計(jì)學(xué)意義。2 mi R-381與臨床病理特征的關(guān)系mi R-381在20例III期和5例IV期結(jié)腸癌中的相對表達(dá)(0.28±0.06)水平明顯低于3例I期和7例II期結(jié)腸癌(1.00±0.12)組織,P0.001。并且mi R-381的表達(dá)還與腫瘤浸潤深度、組織學(xué)分化程度、遠(yuǎn)處轉(zhuǎn)移等因素有關(guān)(P0.05),而與患者性別、年齡因素?zé)o關(guān),與淋巴結(jié)轉(zhuǎn)移數(shù)量無關(guān)。第二部分mi R-381對結(jié)腸癌細(xì)胞生長、增殖和侵襲能力的影響本部分實(shí)驗(yàn)主要利用基因轉(zhuǎn)染、MTT比色法、Brd U法、Transwell小室侵襲實(shí)驗(yàn)和體內(nèi)成瘤的方法檢測沉默mi R-381后結(jié)腸癌細(xì)胞的生長、增殖和侵襲能力。結(jié)果如下:1抑制mi R-381對細(xì)胞在體外生長、增殖和侵襲的影響為明確mi R-381下調(diào)在結(jié)腸癌中的作用,轉(zhuǎn)染了其反義核苷酸至SW480和HCT116細(xì)胞,然后分析細(xì)胞的生長、增殖和侵襲能力。MTT比色法和Brd U摻入實(shí)驗(yàn)顯示,抑制mi R-381顯著促進(jìn)細(xì)胞的生長和增殖能力。此外,這兩種細(xì)胞的浸潤能力也明顯增強(qiáng)。結(jié)果表明,下調(diào)mi R-381能促進(jìn)體外培養(yǎng)的結(jié)腸癌細(xì)胞生長、增殖和侵襲。2抑制mi R-381對腫瘤在裸鼠體內(nèi)生長的影響皮下注射經(jīng)篩選并鑒定穩(wěn)定過表達(dá)mi R-381反義核苷酸或陰性對照的SW480細(xì)胞至裸鼠前肢皮膚。結(jié)果,抑制mi R-381明顯促進(jìn)小鼠體內(nèi)癌細(xì)胞的生長,腫瘤的大小和重量顯著增加。第三部分mi R-381通過靶向LRH-1調(diào)控結(jié)腸癌細(xì)胞的生長、增殖和侵襲本部分研究通過應(yīng)用mi RNA靶基因預(yù)測軟件Target Scan、mi Randa和mi RWalk分析mi R-381的潛在靶基因,發(fā)現(xiàn)mi R-381能夠靶向結(jié)合LRH-13’UTR的ACAUAUA序列,并通過雙熒光素酶報(bào)告基因分析系統(tǒng)驗(yàn)證mi R-381是否與之特異結(jié)合;再以人結(jié)腸癌細(xì)胞株SW480和HCT116為研究對象,應(yīng)用mi R-381沉默和mi R-381過表達(dá)技術(shù)以及Western blot實(shí)驗(yàn),檢測mi R-381對靶基因LRH-1的調(diào)控作用,及沉默LRH-1表達(dá)后結(jié)腸癌細(xì)胞的生長、增殖和侵襲能力。結(jié)果如下:1 mi R-381在結(jié)腸癌細(xì)胞中的靶向調(diào)控基因通過3個生物信息學(xué)軟件,我們預(yù)測并鑒定了mi R-381的調(diào)控靶標(biāo)并揭示其潛在分子機(jī)制。編碼肝受體類似物-1(LRH-1)的基因3’UTR區(qū)域存在一個潛在的mi R-381結(jié)合位點(diǎn)。Western blot實(shí)驗(yàn)表明,抑制mi R-381導(dǎo)致SW480和HCT116細(xì)胞中LRH-1的蛋白水平增加。另外,過表達(dá)mi R-381模擬物降低了這兩種細(xì)胞中LRH-1的表達(dá)。因此,成功克隆了LRH-1基因的3’-UTR非編碼序列,為研究mi R-381是否能與LRH-1基因的3’-UTR非編碼序列特異結(jié)合,我們進(jìn)一步構(gòu)建了突變型3’-UTR非編碼序列,分別插入熒光素酶報(bào)告基因載體。實(shí)驗(yàn)結(jié)果表明,抑制了mi R-381表達(dá)的結(jié)腸癌細(xì)胞株增強(qiáng)了攜帶野生型3’-UTR的熒光素酶活性,但不能增強(qiáng)攜帶突變型3’-UTR的熒光素酶活性。2沉默LRH-1對mi R-381抑癌作用的影響在SW480細(xì)胞中轉(zhuǎn)染了LRH-1 si RNA后,內(nèi)源性LRH-1基因表達(dá)沉默。LRH-1的內(nèi)源性缺失抑制了mi R-381反義核苷酸的促進(jìn)細(xì)胞生長、增殖和侵襲的作用,提示LRH-1對mi R-381在細(xì)胞生長、增殖和侵襲方面有非常重要的作用。結(jié)論:綜合上述三部分內(nèi)容,本研究得出如下結(jié)論:1 mi R-381在人結(jié)腸癌組織中顯著下調(diào),mi R-381的表達(dá)降低與結(jié)腸癌臨床分期有關(guān)。2體外和體內(nèi)研究進(jìn)一步表明,抑制mi R-381促進(jìn)結(jié)腸癌細(xì)胞的生長、增殖和侵襲,同時促進(jìn)裸鼠體內(nèi)腫瘤的生長。3 LRH-1是mi R-381的靶基因,mi R-381的下調(diào)在結(jié)腸癌的發(fā)生發(fā)展過程中起著重要的作用。4 mi R-381是結(jié)腸癌發(fā)生發(fā)展過程中一個重要的生物標(biāo)志物,具有靶向LRH-1治療癌癥的潛能。
[Abstract]:Colon cancer is a common malignant tumor, which is an individual disease of multiple gene expression disorders that occur under the effects of internal and external factors, which is a serious threat to the health of human life. Although a large number of studies have confirmed that diet and genetic factors play an important role in the occurrence and development of colon cancer, the key factors for malignant transformation of colon cancer and the proliferation and invasion of tumor cells are still to be further studied and determined. MicroRNAs (micro RNAs, mi RNA) are a class of RNA with a length of about 19-22 nucleotides and regulate the post-transcriptional expression by complementary matching with the 3 '-UTR non-coding region of the target gene m RNA. This interaction results in translation repression, in most cases the level of expression of m-RNA. The study shows that the expression of multiple mi-RNA in human tumors is down-regulated or up-regulated, including colon cancer, which provides a new molecular basis for tumorigenesis. Tang et al. first reported the role of mi R-381 in glioma cells. The results show that mi R-381 can promote the proliferation of glioma cells in vitro and in vivo, which is related to the inhibition of MEK/ ERK and AKT signals. However, Rothschild et al. found that the expression of mi R-381 in lung adenocarcinoma was significantly reduced, and the low mi R-381 expression level was associated with poor prognosis. In addition, mi R-381 enhances the chemotherapy sensitivity of 5-FU in renal cancer cells by up-regulating the activity of Cdc2. The expression of mi R-381 was also negatively correlated with the expression of MDR1 gene and the development of multiple drug resistance. The results show that the role of mi R-381 in cancer cells is different from that of the tumor. Therefore, it is necessary to study the biological function of mi R-381 in the colon cancer and to open up a new research path for the in-depth understanding of the occurrence and development of colon cancer. Objective: To study the effect of mi R-381 on the growth, proliferation and invasion of colon cancer cells, and then to predict and verify the target gene of mi R-381. The role of mi R-381 in the development of colon cancer is described, and the experimental basis for the further understanding of the potential molecular mechanism of colon cancer and the development of new effective molecular therapy target is provided. Methods: The expression of mi R-381 and the expression of mi R-381 in different clinical stages and their relationship with the clinicopathological features were observed by RT-PCR. The effects of mi R-381 on the growth, proliferation and invasion of colon cancer cell lines were observed by using the RNA interference technique to silence the expression of mi R-381. The potential target gene of mi R-381 was analyzed by using the mi-RNA target gene prediction software, Target Scan, mi rana and mi RWalk, and the mi R-381 was found to be able to target the ACAUAUA sequence of LRH-1 3 'UTR, and verified whether the mi R-381 was specifically bound to it by the double-luciferase reporter gene analysis. The effects of mi R-381 and mi R-381 on the expression of LRH-1 in human colon cancer cell line SW480 and HCT116 were studied. The effect of mi R-381 on the expression of human colon cancer cell line LRH-1 was observed, and the effect of mi R-381 on the expression of mi R-381 was observed by using the RNA interference technique to silence the expression of LRH-1. Results: The specific results of the three parts of the subject are as follows: The first part mi R-381 is the expression of the first part mi R-381 in the colon cancer tissue and the adjacent tissue, and the expression of the mi R-381 in the clinical resection of the colon cancer specimen and the adjacent tissue is observed by the fluorescence quantitative RT-PCR method. The results are as follows:1 mi R-381 expression in colon cancer tissue RT-PCR results show that the relative expression level of mi R-381 in the colon cancer tissue (0.50-0.08) is significantly reduced, and is 0.5 times that of the adjacent tissue (1.00-0.13). The relative expression of mi R-381 in 20 patients with stage III and 5 patients with stage IV colon cancer (0.28-0.06) was significantly lower than that of 3 patients with stage I and 7 cases of colon cancer (1.00-0.12), P 0.001. The expression of mi R-381 was related to the depth of tumor invasion, the degree of histological differentiation, distant metastasis and other factors (P0.05), but not related to the patient's sex and age, regardless of the number of lymph node metastasis. The effects of the second part of mi R-381 on the growth, proliferation and invasion of colon cancer cells were mainly used to detect the growth, proliferation and invasion of the colon cancer cells after the silent mi R-381 was detected by the methods of gene transfection, MTT colorimetric method, Brd U method, Transwell chamber invasion experiment and in vivo tumorigenesis. The results are as follows:1. The effect of the inhibition of mi R-381 on the growth, proliferation and invasion of the cells in vitro is the effect of down-regulation of mi R-381 in the colon cancer, and the antisense nucleus of the cells is transfected into the SW480 and HCT116 cells, and then the growth, proliferation and invasion ability of the cells are analyzed. MTT and BrdU incorporation experiments showed that the inhibition of mi R-381 significantly promoted the growth and proliferation of cells. In addition, the infiltration capacity of both cells was also enhanced. The results showed that the down-regulation of mi R-381 could promote the growth, proliferation and invasion of colon cancer cells cultured in vitro. As a result, the inhibition of mi R-381 significantly promoted the growth of cancer cells in the mice, and the size and weight of the tumor significantly increased. The third part mi R-381, by targeting the growth, proliferation and invasion of colon cancer cells by targeting LRH-1, studies the potential target genes of mi R-381 by using the mi-RNA target gene prediction software, Target Scan, mi rana and mi RWk, and found that mi R-381 is capable of targeting the ACAUAUA sequence in combination with LRH-13 'UTR, The expression of mi R-381 and mi R-381 in human colon cancer cell line SW480 and HCT116 and Western blot were used to detect the regulatory effects of mi R-381 on the target gene LRH-1. And the growth, proliferation and invasion ability of colon cancer cells after the expression of the silent LRH-1. The results are as follows:1 mi R-381 targeting regulatory gene in colon cancer cells has passed 3 bioinformatics software, and we predict and identify the regulatory target of mi R-381 and reveal its potential molecular mechanism. A potential mi R-381 binding site is present in the 3 'UTR region of the gene encoding the hepatic receptor analog-1 (LRH-1). Western blot showed that the inhibition of mi R-381 resulted in an increase in the protein level of LRH-1 in SW480 and HCT116 cells. In addition, the overexpression of mi R-381 mimics the expression of LRH-1 in both cells. Therefore, the non-coding sequence of the 3 '-UTR of the LRH-1 gene is successfully cloned, and the mutant type 3'-UTR non-coding sequence is further constructed to be inserted into the luciferase reporter gene vector for studying whether the mi R-381 can be specifically combined with the 3 '-UTR non-coding sequence of the LRH-1 gene. The results showed that the expression of mi R-381 in the colon cancer cell line enhanced the luciferase activity carrying the wild type 3 '-UTR, but could not enhance the luciferase activity carrying the mutant 3'-UTR. The effect of the silence LRH-1 on the anti-cancer of the mi R-381 was after the LRH-1si RNA was transfected into the SW480 cell, The endogenous LRH-1 gene expression was silent. The endogenous deletion of LRH-1 inhibits the growth, proliferation and invasion of mi R-381 antisense, and suggests that LRH-1 plays a very important role in cell growth, proliferation and invasion. Conclusion: The conclusion is as follows:1 mi R-381 is significantly down-regulated in human colon cancer tissue, and the expression of mi R-381 is associated with the clinical stage of colon cancer. In vitro and in vivo studies have further shown that the inhibition of mi R-381 promotes the growth, proliferation and invasion of colon cancer cells, 3LRH-1 is the target gene of mi R-381, and the down-regulation of mi R-381 plays an important role in the development of colon cancer.4 mi R-381 is an important biomarker in the development of colon cancer, and has the potential to target LRH-1 for cancer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R692
本文編號：2484499
[Abstract]:Colon cancer is a common malignant tumor, which is an individual disease of multiple gene expression disorders that occur under the effects of internal and external factors, which is a serious threat to the health of human life. Although a large number of studies have confirmed that diet and genetic factors play an important role in the occurrence and development of colon cancer, the key factors for malignant transformation of colon cancer and the proliferation and invasion of tumor cells are still to be further studied and determined. MicroRNAs (micro RNAs, mi RNA) are a class of RNA with a length of about 19-22 nucleotides and regulate the post-transcriptional expression by complementary matching with the 3 '-UTR non-coding region of the target gene m RNA. This interaction results in translation repression, in most cases the level of expression of m-RNA. The study shows that the expression of multiple mi-RNA in human tumors is down-regulated or up-regulated, including colon cancer, which provides a new molecular basis for tumorigenesis. Tang et al. first reported the role of mi R-381 in glioma cells. The results show that mi R-381 can promote the proliferation of glioma cells in vitro and in vivo, which is related to the inhibition of MEK/ ERK and AKT signals. However, Rothschild et al. found that the expression of mi R-381 in lung adenocarcinoma was significantly reduced, and the low mi R-381 expression level was associated with poor prognosis. In addition, mi R-381 enhances the chemotherapy sensitivity of 5-FU in renal cancer cells by up-regulating the activity of Cdc2. The expression of mi R-381 was also negatively correlated with the expression of MDR1 gene and the development of multiple drug resistance. The results show that the role of mi R-381 in cancer cells is different from that of the tumor. Therefore, it is necessary to study the biological function of mi R-381 in the colon cancer and to open up a new research path for the in-depth understanding of the occurrence and development of colon cancer. Objective: To study the effect of mi R-381 on the growth, proliferation and invasion of colon cancer cells, and then to predict and verify the target gene of mi R-381. The role of mi R-381 in the development of colon cancer is described, and the experimental basis for the further understanding of the potential molecular mechanism of colon cancer and the development of new effective molecular therapy target is provided. Methods: The expression of mi R-381 and the expression of mi R-381 in different clinical stages and their relationship with the clinicopathological features were observed by RT-PCR. The effects of mi R-381 on the growth, proliferation and invasion of colon cancer cell lines were observed by using the RNA interference technique to silence the expression of mi R-381. The potential target gene of mi R-381 was analyzed by using the mi-RNA target gene prediction software, Target Scan, mi rana and mi RWalk, and the mi R-381 was found to be able to target the ACAUAUA sequence of LRH-1 3 'UTR, and verified whether the mi R-381 was specifically bound to it by the double-luciferase reporter gene analysis. The effects of mi R-381 and mi R-381 on the expression of LRH-1 in human colon cancer cell line SW480 and HCT116 were studied. The effect of mi R-381 on the expression of human colon cancer cell line LRH-1 was observed, and the effect of mi R-381 on the expression of mi R-381 was observed by using the RNA interference technique to silence the expression of LRH-1. Results: The specific results of the three parts of the subject are as follows: The first part mi R-381 is the expression of the first part mi R-381 in the colon cancer tissue and the adjacent tissue, and the expression of the mi R-381 in the clinical resection of the colon cancer specimen and the adjacent tissue is observed by the fluorescence quantitative RT-PCR method. The results are as follows:1 mi R-381 expression in colon cancer tissue RT-PCR results show that the relative expression level of mi R-381 in the colon cancer tissue (0.50-0.08) is significantly reduced, and is 0.5 times that of the adjacent tissue (1.00-0.13). The relative expression of mi R-381 in 20 patients with stage III and 5 patients with stage IV colon cancer (0.28-0.06) was significantly lower than that of 3 patients with stage I and 7 cases of colon cancer (1.00-0.12), P 0.001. The expression of mi R-381 was related to the depth of tumor invasion, the degree of histological differentiation, distant metastasis and other factors (P0.05), but not related to the patient's sex and age, regardless of the number of lymph node metastasis. The effects of the second part of mi R-381 on the growth, proliferation and invasion of colon cancer cells were mainly used to detect the growth, proliferation and invasion of the colon cancer cells after the silent mi R-381 was detected by the methods of gene transfection, MTT colorimetric method, Brd U method, Transwell chamber invasion experiment and in vivo tumorigenesis. The results are as follows:1. The effect of the inhibition of mi R-381 on the growth, proliferation and invasion of the cells in vitro is the effect of down-regulation of mi R-381 in the colon cancer, and the antisense nucleus of the cells is transfected into the SW480 and HCT116 cells, and then the growth, proliferation and invasion ability of the cells are analyzed. MTT and BrdU incorporation experiments showed that the inhibition of mi R-381 significantly promoted the growth and proliferation of cells. In addition, the infiltration capacity of both cells was also enhanced. The results showed that the down-regulation of mi R-381 could promote the growth, proliferation and invasion of colon cancer cells cultured in vitro. As a result, the inhibition of mi R-381 significantly promoted the growth of cancer cells in the mice, and the size and weight of the tumor significantly increased. The third part mi R-381, by targeting the growth, proliferation and invasion of colon cancer cells by targeting LRH-1, studies the potential target genes of mi R-381 by using the mi-RNA target gene prediction software, Target Scan, mi rana and mi RWk, and found that mi R-381 is capable of targeting the ACAUAUA sequence in combination with LRH-13 'UTR, The expression of mi R-381 and mi R-381 in human colon cancer cell line SW480 and HCT116 and Western blot were used to detect the regulatory effects of mi R-381 on the target gene LRH-1. And the growth, proliferation and invasion ability of colon cancer cells after the expression of the silent LRH-1. The results are as follows:1 mi R-381 targeting regulatory gene in colon cancer cells has passed 3 bioinformatics software, and we predict and identify the regulatory target of mi R-381 and reveal its potential molecular mechanism. A potential mi R-381 binding site is present in the 3 'UTR region of the gene encoding the hepatic receptor analog-1 (LRH-1). Western blot showed that the inhibition of mi R-381 resulted in an increase in the protein level of LRH-1 in SW480 and HCT116 cells. In addition, the overexpression of mi R-381 mimics the expression of LRH-1 in both cells. Therefore, the non-coding sequence of the 3 '-UTR of the LRH-1 gene is successfully cloned, and the mutant type 3'-UTR non-coding sequence is further constructed to be inserted into the luciferase reporter gene vector for studying whether the mi R-381 can be specifically combined with the 3 '-UTR non-coding sequence of the LRH-1 gene. The results showed that the expression of mi R-381 in the colon cancer cell line enhanced the luciferase activity carrying the wild type 3 '-UTR, but could not enhance the luciferase activity carrying the mutant 3'-UTR. The effect of the silence LRH-1 on the anti-cancer of the mi R-381 was after the LRH-1si RNA was transfected into the SW480 cell, The endogenous LRH-1 gene expression was silent. The endogenous deletion of LRH-1 inhibits the growth, proliferation and invasion of mi R-381 antisense, and suggests that LRH-1 plays a very important role in cell growth, proliferation and invasion. Conclusion: The conclusion is as follows:1 mi R-381 is significantly down-regulated in human colon cancer tissue, and the expression of mi R-381 is associated with the clinical stage of colon cancer. In vitro and in vivo studies have further shown that the inhibition of mi R-381 promotes the growth, proliferation and invasion of colon cancer cells, 3LRH-1 is the target gene of mi R-381, and the down-regulation of mi R-381 plays an important role in the development of colon cancer.4 mi R-381 is an important biomarker in the development of colon cancer, and has the potential to target LRH-1 for cancer.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R692
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1 李夏雨;沈守榮;武明花;李小玲;熊煒;盧建紅;周鳴;馬健;向娟娟;曾朝陽;向波;周艷宏;肖嵐;周厚德;范松青;李桂源;;多基因遺傳性腫瘤不同階段轉(zhuǎn)錄組學(xué)調(diào)控規(guī)律及其分子機(jī)制[J];中南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2011年07期
2 Carl Christoph Schimanski;Kirsten Frerichs;Fareed Rahman;Martin Berger;Hauke Lang;Peter R Galle;Markus Moehler;Ines Gockel;;High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells[J];World Journal of Gastroenterology;2009年17期
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