本文選題：肺癌 + miRNA��； 參考：《鄭州大學(xué)》2016年博士論文

【摘要】：背景及目的肺癌是嚴(yán)重威脅人類生命健康的惡性腫瘤,己經(jīng)成為全球癌癥相關(guān)死亡的主要原因。肺癌可分為小細(xì)胞肺癌(SCLC)和非小細(xì)胞肺癌(NSCLC)兩類。手術(shù)、化療、靶向治療及放療是肺癌的主要治療手段。盡管目前肺癌的診治水平不斷進(jìn)步,但肺癌患者長(zhǎng)期生存并不樂(lè)觀,總體5年生存率只有10%-20%。局部復(fù)發(fā)和遠(yuǎn)處轉(zhuǎn)移是導(dǎo)致肺癌患者死亡的主要原因。肺癌的發(fā)生、發(fā)展是多基因改變共同作用的結(jié)果,涉及到多種癌基因的激活和抑癌基因的失活。目前基因靶向治療己經(jīng)成為肺癌研究的新熱點(diǎn),發(fā)現(xiàn)和認(rèn)識(shí)新的治療靶點(diǎn)并用于肺癌的診斷和治療,具有重要的臨床價(jià)值及重大的現(xiàn)實(shí)意義。微小RNA(miRNA,microRNA)長(zhǎng)度為19-25個(gè)核苷酸的小非編碼RNA,廣泛存在于動(dòng)植物體內(nèi),影響許多蛋白編碼基因的表達(dá)。miRNA通過(guò)與靶m RNA特異結(jié)合可以抑制靶m RNA翻譯或降解靶m RNA。miRNA參與調(diào)控細(xì)胞分化、增殖、生長(zhǎng)、遷移、凋亡等許多細(xì)胞行為。miRNA表達(dá)異常在腫瘤發(fā)生、進(jìn)展和復(fù)發(fā)中發(fā)揮重要作用,扮演著抑癌或促進(jìn)癌癥的作用。miR-9、miR-92b、miR-224和miR-183等為癌基因并促進(jìn)肺癌轉(zhuǎn)移。miR-101、miR-133a和miR-141等為抑癌基因,可以顯著抑制肺癌細(xì)胞轉(zhuǎn)移。此外,與肺癌相關(guān)的存在于血液,血清,血漿和唾液中的miRNA同樣在肺癌中發(fā)揮著重要的作用,使miRNA成為一種新的腫瘤標(biāo)志物。整合素(integrin,ITGB)屬于細(xì)胞表面分子,是一類由α和β亞基以非共價(jià)鍵形式結(jié)合組成的跨膜蛋白受體,介導(dǎo)細(xì)胞之間以及細(xì)胞與細(xì)胞外基質(zhì)(extracellular matrix,ECM)的粘附。整合素因其跨膜結(jié)構(gòu)的特殊性而具有雙向信號(hào)轉(zhuǎn)導(dǎo)功能。目前已發(fā)現(xiàn)18種α亞基和8種β亞基,可形成24種異源二聚體,分布于全身不同組織和器官,發(fā)揮各自的生物學(xué)功能。同時(shí),整合素也與疾病的發(fā)生和發(fā)展密切相關(guān),其信號(hào)轉(zhuǎn)導(dǎo)途徑也能參與腫瘤的發(fā)生和發(fā)展。整合素的突變或異常表達(dá)通常被認(rèn)為與腫瘤的發(fā)生和轉(zhuǎn)移相關(guān)。整合素β3(integrin beta3,ITGB3)屬于β亞基中的一員,在全身不同組織中均有表達(dá),參與多種生物學(xué)過(guò)程,發(fā)揮不同的生理功能。ITGB3是多種蛋白質(zhì)(諸如纖維粘連蛋白、層粘連蛋白、基質(zhì)金屬蛋白酶-2、骨調(diào)蛋白和玻連蛋白)的共同受體。已在各種惡性腫瘤中觀察到ITGB3表達(dá)高度升高。ITGB3對(duì)于急性粒細(xì)胞性白血病(Acute myeloid leukemia,AML)發(fā)生發(fā)揮關(guān)鍵作用,使其成為潛在治療靶點(diǎn)。有研究證實(shí)ITGB3是誘發(fā)結(jié)直腸癌細(xì)胞遷移和侵襲的一種重要調(diào)節(jié)因子。在乳腺癌中,m RNA表達(dá)譜排列表明,轉(zhuǎn)移性腫瘤細(xì)胞的一些血管生成相關(guān)蛋白(包括ITGB3)顯著上調(diào)。此外,最新研究證明,肺癌組織中表達(dá)下調(diào)的let-7c,通過(guò)靶向作用于ITGB3抑制肺癌細(xì)胞的遷移和侵襲。miR-338家族(miR-338,miR-338-3p,miR-338-5p)位于凋亡相關(guān)酪氨酸激酶7號(hào)內(nèi)含子上。已經(jīng)證實(shí)miR-338在肝細(xì)胞癌、口腔癌和食管鱗狀細(xì)胞癌中表達(dá)下調(diào)。miR-338過(guò)度表達(dá)可以抑制胃癌細(xì)胞增殖并促進(jìn)細(xì)胞凋亡。肝細(xì)胞癌中的miR-338水平恢復(fù)可使癌細(xì)胞對(duì)索拉非尼治療敏感。研究已經(jīng)證實(shí),miR-338能夠通過(guò)靶向作用于Smoothened抑制結(jié)直腸癌細(xì)胞侵襲和遷移。但仍然不清楚miR-338在肺癌轉(zhuǎn)移中的作用機(jī)制。在本研究中,我們嘗試使用實(shí)時(shí)熒光PCR(q RT-PCR)檢測(cè)評(píng)估5個(gè)肺癌細(xì)胞株、1個(gè)人肺成纖維細(xì)胞MRC-5細(xì)胞株及115例肺癌組織、癌旁正常肺組織中miR-338的表達(dá)。構(gòu)建miR-338過(guò)表達(dá)肺癌細(xì)胞株,探索在體外環(huán)境下miR-338對(duì)肺癌細(xì)胞增殖、粘附、遷移及侵襲的影響。并檢測(cè)miR-338過(guò)表達(dá)肺癌細(xì)胞株中ITGB3蛋白質(zhì)的表達(dá),初步研究miR-338抑制肺癌轉(zhuǎn)移的分子靶向作用機(jī)制。本課題包含以下三個(gè)部分:第一部分:miR-338在肺癌細(xì)胞株及肺癌組織中的表達(dá)及意義;第二部分:上調(diào)miR-338表達(dá)對(duì)肺癌細(xì)胞株A549、NCI-H292生物學(xué)行為的影響;第三部分:miR-338通過(guò)靶向作用于整合素β3抑制肺癌轉(zhuǎn)移。第一部分miR-338在肺癌細(xì)胞株及肺癌組織中的表達(dá)及意義方法:1、培養(yǎng)5個(gè)肺癌細(xì)胞株(A549、NCI-H292、NCI-H460、NCI-H446、NCI-H1299)和1個(gè)人肺成纖維細(xì)胞MRC-5細(xì)胞株。2、收集手術(shù)切除的115例肺癌組織及相對(duì)應(yīng)的癌旁正常肺組織標(biāo)本。3、提取所有細(xì)胞株和115例肺癌組織及相對(duì)應(yīng)的癌旁正常肺組織的RNA,并用q RT-PCR檢測(cè)miR-338的表達(dá)。4、分析肺癌組織中的miR-338表達(dá)與患者性別、年齡、吸煙史、腫瘤大小、腫瘤癌栓、淋巴結(jié)轉(zhuǎn)移、腫瘤復(fù)發(fā)及TNM分期之間的相關(guān)性。5、使用SPSS 13.0對(duì)數(shù)據(jù)進(jìn)行分析,并以平均值±標(biāo)準(zhǔn)差的形式表示。使用配對(duì)樣本t檢驗(yàn)估計(jì)兩組間差異。使用單因素方差分析(ANOVA)分析miR-338表達(dá)與臨床病理因素之間關(guān)系,并使用對(duì)數(shù)秩檢驗(yàn)根據(jù)Kaplan-Meier法劃出生存曲線。如果p0.05,則認(rèn)為組間差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、與人肺成纖維細(xì)胞MRC-5細(xì)胞相比,所有肺癌細(xì)胞株中的miR-338表達(dá)顯著下調(diào)(A549 1.0vs0.15±0.01、NCI-H292 1.0vs0.35±0.12、NCI-H4601.0vs0.3±0.02、NCI-H446 1.0vs0.25±0.07、NCI-H1299 1.0vs0.275±0.01,p0.05)。2、與癌旁正常肺組織相比,115例肺癌組織中的miR-338表達(dá)顯著下調(diào)(0vs-2.99±3.69,p0.001)。肺癌組織中的miR-338表達(dá)降低與患者性別、年齡、吸煙史、腫瘤大小和淋巴結(jié)轉(zhuǎn)移無(wú)關(guān)(p0.05)。miR-338表達(dá)降低與腫瘤癌栓、腫瘤復(fù)發(fā)、TNM分期相關(guān)(p值分別為0.005、0.004、0.025)。低miR-338表達(dá)組的5年總生存率顯著低于高miR-338表達(dá)組(中位生存時(shí)間44個(gè)月vs53個(gè)月,P=0.001)。第二部分:上調(diào)miR-338表達(dá)對(duì)肺癌細(xì)胞株A549、NCI-H292生物學(xué)行為的影響方法:1、構(gòu)建、培養(yǎng)重組miR-338慢病毒感染的A549、NCI-H292細(xì)胞細(xì)胞株,用q RT-PCR檢測(cè)細(xì)胞中miR-338的表達(dá)。2、CCK-8法檢測(cè)重組miR-338慢病毒感染的A549、NCI-H292細(xì)胞及對(duì)照細(xì)胞增殖和生長(zhǎng)能力。3、檢測(cè)重組miR-338慢病毒感染的A549、NCI-H292細(xì)胞及對(duì)照細(xì)胞粘附能力。4、Transwell小室實(shí)驗(yàn)檢測(cè)重組miR-338慢病毒感染的A549、NCI-H292細(xì)胞及對(duì)照細(xì)胞的遷移及侵襲能力。5、裸鼠移植瘤模型實(shí)驗(yàn)檢測(cè)重組miR-338慢病毒感染的NCI-H292細(xì)胞及對(duì)照細(xì)胞對(duì)裸鼠肺移植瘤的影響。6、使用SPSS 13.0對(duì)數(shù)據(jù)進(jìn)行分析,并以平均值±標(biāo)準(zhǔn)差的形式表示。使用配對(duì)樣本t檢驗(yàn)估計(jì)兩組間差異。如果p0.05,則認(rèn)為組間差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、重組miR-338慢病毒感染的A549、NCI-H292細(xì)胞較對(duì)照細(xì)胞miR-338的表達(dá)明顯升高(A549 646.37±35.45vs23.05±3.56、NCI-H292330.86±11.05vs10.54±2.35,P0.05)。成功構(gòu)建了高表達(dá)miR-338的肺癌細(xì)胞株。2、在體外環(huán)境下上調(diào)miR-338的表達(dá)可以抑制A549、NCI-H292肺癌細(xì)胞的增殖(P0.05)、粘附(A549平均細(xì)胞計(jì)數(shù)1233±249vs310±22,p=0.035)(NCI-H292平均細(xì)胞計(jì)數(shù)180±16vs72±10,p=0.028)、遷移(A549平均細(xì)胞計(jì)數(shù)347±41vs190±8,p=0.029)(NCI-H292平均細(xì)胞計(jì)數(shù)287±33vs127±21,p=0.045)及侵襲能力(A549平均細(xì)胞計(jì)數(shù)197±12vs68±14,p=0.008)(NCI-H292平均細(xì)胞計(jì)數(shù)106±10vs41±3,p=0.006)。3、裸鼠異種移植腫瘤模型實(shí)驗(yàn)表明,miR-338高表達(dá)能有效地抑制裸鼠肺移植瘤的生長(zhǎng)(平均腫瘤克隆數(shù)20±7vs4±2,p=0.004)。第三部分miR-338通過(guò)靶向作用于整合素β3抑制肺癌轉(zhuǎn)移方法:1、生物信息學(xué)分析推測(cè)ITGB3為miR-338靶基因。2、用Western免疫印跡檢測(cè)miR-338過(guò)度表達(dá)肺癌細(xì)胞株A549和NCI-H292及對(duì)照細(xì)胞中的ITGB3蛋白質(zhì)表達(dá)。3、雙熒光素酶報(bào)告檢測(cè)驗(yàn)證miR-338靶基因。4、使用SPSS 13.0對(duì)數(shù)據(jù)進(jìn)行分析,并以平均值±標(biāo)準(zhǔn)差的形式表示。使用配對(duì)樣本t檢驗(yàn)估計(jì)兩組間差異。如果p0.05,則認(rèn)為組間差異具有統(tǒng)計(jì)學(xué)意義。結(jié)果:1、miR-338過(guò)表達(dá)肺癌細(xì)胞株A549和NCI-H292中的ITGB3蛋白質(zhì)表達(dá)較對(duì)照細(xì)胞均明顯降低(A549 1.0vs0.35±0.04,p0.001)(NCI-H2921.0vs0.69±0.07,p=0.01)。2、雙熒光素酶報(bào)告檢測(cè)結(jié)果顯示miR-338過(guò)表達(dá)組的熒光素酶活性較對(duì)照組降低(A549 1.0vs0.75±0.08,p=0.03)(NCI-H292 1.0vs0.62±0.06,p=0.008)。結(jié)論:1、在肺癌細(xì)胞株及肺癌組織中,miR-338表達(dá)水平較正常細(xì)胞及組織顯著降低。在肺癌組織中miR-338表達(dá)水平與患者性別、年齡、吸煙史、腫瘤大小和淋巴結(jié)轉(zhuǎn)移無(wú)關(guān),而與腫瘤癌栓、腫瘤復(fù)發(fā)、TNM分期相關(guān)。低miR-338表達(dá)組的5年總生存率顯著低于高miR-338表達(dá)組。2、體外上調(diào)肺癌細(xì)胞中miR-338表達(dá)水平可有效抑制肺癌細(xì)胞的增殖、粘附能力,降低肺癌細(xì)胞的遷移和侵襲能力。3、miR-338是通過(guò)作用于靶基因ITGB3 mRNA3’UTR區(qū),從而對(duì)其表達(dá)產(chǎn)生負(fù)調(diào)控作用。miR-338發(fā)揮抑癌作用。ITGB3是一種新的miR-338肺癌靶基因,為肺癌基因治療潛在的新靶點(diǎn)。
[Abstract]:Background and objective lung cancer is a malignant tumor that seriously threatens human life and health. It has become the main cause of global cancer related death. Lung cancer can be divided into two categories: small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC). Surgery, chemotherapy, targeted therapy and radiotherapy are the main treatment methods for lung cancer. Although the diagnosis and treatment of lung cancer is constantly at present Progress, but the long-term survival of lung cancer patients is not optimistic. The overall 5 year survival rate is only 10%-20%. local recurrence and distant metastasis is the main cause of the death of lung cancer patients. The development of lung cancer is the result of the common effect of multiple gene changes, involving the activation of a variety of oncogenes and the inactivation of tumor suppressor genes. It has become a new hot spot in the research of lung cancer. It is of important clinical value and great practical significance to discover and recognize new therapeutic targets and to be used in the diagnosis and treatment of lung cancer. Small RNA (miRNA, microRNA) is a small noncoding RNA with 19-25 nucleotides in length, which is widely used in animals and plants and affects the expression of many protein encoded genes in.MiRNA Specific binding to target m RNA can inhibit target m RNA translation or degradation of target m RNA.miRNA to participate in the regulation of cell differentiation, proliferation, growth, migration, apoptosis and many other cellular.MiRNA expressions, which play an important role in tumor occurrence, progression and recurrence, playing the role of cancer inhibiting or promoting cancer, miR-92b, miR-224 and miR-183, and so on. The oncogene and promoting the metastasis of lung cancer,.MiR-101, miR-133a and miR-141 as tumor suppressor genes, can significantly inhibit the metastasis of lung cancer cells. In addition, the miRNA associated with lung cancer in the blood, serum, plasma and saliva also plays an important role in lung cancer, making miRNA a new tumor marker. Integrin (integrin, ITGB). Cell surface molecules, a class of transmembrane protein receptors composed of alpha and beta subunits, which are composed of non covalent bonds, mediate adhesion between cells and cells and the extracellular matrix (extracellular matrix, ECM). Integrins have bi-directional signal transduction function because of their transmembrane structure. 18 subunits and 8 beta subunits have been found. It can form 24 kinds of heterologous two polymers, distributed in different tissues and organs of the whole body, and play their respective biological functions. At the same time, integrin is also closely related to the occurrence and development of disease, and its signal transduction pathway can also participate in the occurrence and development of tumor. Integrin beta 3 (integrin beta3, ITGB3), a member of the beta subunit, is expressed in various tissues throughout the body, participates in a variety of biological processes and plays a different physiological function,.ITGB3 is a common receptor for a variety of proteins, such as fibronectin, laminin, matrix metalloproteinase -2, osteosin and bosin protein. A high elevation of ITGB3 expression is observed in various malignant tumors and.ITGB3 plays a key role in the occurrence of acute myelocytic leukemia (Acute myeloid leukemia, AML), making it a potential therapeutic target. Studies have shown that ITGB3 is an important regulator of the migration and invasion of colorectal cancer cells. In breast cancer, the RNA expression profile of M The list shows that some angiogenesis related proteins (including ITGB3) are significantly up-regulated in metastatic tumor cells. In addition, the latest research has shown that Let-7c, expressed in lung cancer tissue, can inhibit the migration and invasion of lung cancer cells by targeting ITGB3 (miR-338, miR-338-3p, miR-338-5p) in the.MiR-338 family (miR-338, miR-338-3p, miR-338-5p) in the apoptosis related tyrosine kinase No. On the intron. It has been confirmed that the overexpression of miR-338 in the hepatocellular carcinoma, oral and esophageal squamous cell carcinoma can inhibit the proliferation of gastric cancer cells and promote cell apoptosis. The recovery of miR-338 in hepatocellular carcinoma can make the cancer cells sensitive to the Sola Fini treatment. The research has confirmed that miR-338 can be targeted by the target. Smoothened inhibits the invasion and migration of colorectal cancer cells. But it is still unclear how miR-338 plays a role in the metastasis of lung cancer. In this study, we tried to evaluate 5 lung cancer cell lines, 1 pulmonary fibroblasts MRC-5 cell lines, 115 lung cancer tissues, and 115 lung cancer tissues, and miR-338 in normal lung tissues by using real-time fluorescence PCR (Q RT-PCR) detection. To express the expression of miR-338 over expression of lung cancer cell lines, explore the effect of miR-338 on proliferation, adhesion, migration and invasion of lung cancer cells in vitro, and detect the expression of ITGB3 protein in miR-338 overexpressed lung cancer cell lines, and preliminary study the molecular targeting mechanism of miR-338 to inhibit the metastasis of lung cancer. This topic includes the following three parts: Part one: expression and significance of miR-338 in lung cancer cell lines and lung cancer tissues; the second part: the effect of up regulation of miR-338 expression on the biological behavior of lung cancer cell line A549 and NCI-H292; the third part: miR-338 inhibits metastasis of lung cancer by targeting integrin beta 3. The expression of first division miR-338 in lung cancer cell lines and lung cancer tissues Significance methods: 1, 5 lung cancer cell lines (A549, NCI-H292, NCI-H460, NCI-H446, NCI-H1299) and 1 individual pulmonary fibroblast MRC-5 cell lines.2 were used to collect 115 cases of surgically removed lung cancer tissues and corresponding normal lung tissue specimens adjacent to the cancerous lung tissue, and extract all the cell lines and 115 cases of lung cancer tissue and the corresponding normal lung tissue adjacent to the cancerous lung tissues. The expression of.4 in miR-338 was detected by Q RT-PCR, and the correlation between miR-338 expression in lung cancer tissues and the sex, age, smoking history, tumor size, tumor tumor thrombus, lymph node metastasis, tumor recurrence and TNM staging were analyzed, and the data were analyzed with SPSS 13 and expressed in the form of mean mean standard deviation. The paired sample t test was used. A single factor variance analysis (ANOVA) was used to analyze the relationship between the miR-338 expression and the clinicopathological factors, and the logarithmic rank test was used to draw a survival curve according to the Kaplan-Meier method. If P0.05, the difference between the groups was statistically significant. Results: 1, all lung cancer cells were thinner than the human lung fibroblast MRC-5 cells. The expression of miR-338 in the cell lines was significantly down (A549 1.0vs0.15 + 0.01, NCI-H292 1.0vs0.35 + 0.12, NCI-H4601.0vs0.3 + 0.02, NCI-H446 1.0vs0.25 + 0.07, NCI-H1299 1.0vs0.275 + 0.01, P0.05).2. Compared with normal lung tissue adjacent to the carcinoma, 115 cases of lung cancer tissues were significantly down regulated. The decrease of expression was not related to the sex, age, smoking history, tumor size and lymph node metastasis (P0.05).MiR-338 expression decreased with tumor thrombus, tumor recurrence, and TNM staging (P value was 0.005,0.004,0.025). The total 5 year survival rate of low miR-338 expression group was significantly lower than that of high miR-338 expression group (median survival time was 44 months vs53 months, P=0.001 The second part: the second part: up regulation of the effects of miR-338 expression on the biological behavior of lung cancer cell line A549, NCI-H292, 1, construction, culture of A549, NCI-H292 cell lines, Q RT-PCR detection of miR-338 expression.2, CCK-8 method for detecting recombinant lentivirus infection Colonization and growth capacity.3, the adhesion ability of recombinant miR-338 lentivirus infection A549, NCI-H292 cells and control cells.4, Transwell chamber test to detect the A549 of recombinant miR-338 lentivirus infection, the migration and invasion ability of NCI-H292 cells and control cells,.5, nude mice transplantation tumor model test for the detection of recombinant miR-338 lentivirus infection NCI-H292 The effect of cell and control cells on lung xenografts in nude mice.6, SPSS 13 was used to analyze the data and expressed in the form of mean standard deviation. The difference between the two groups was estimated by paired sample t test. If P0.05, the difference between the groups was statistically significant. Results: 1, the A549 of recombinant miR-338 lentivirus infection, NCI-H292 cells were compared. The expression of miR-338 in the control cells increased significantly (A549 646.37 + 35.45vs23.05 + 3.56, NCI-H292330.86 + 11.05vs10.54 + 2.35, P0.05). The lung cancer cell line with high expression of miR-338 was successfully constructed. The expression of miR-338 under the environment in vitro could inhibit the proliferation of A549, NCI-H292 lung cancer cells (P0.05), and the average cell count was 1233 + 249. Vs310 + 22, p=0.035) (average cell count of NCI-H292 180 + 16vs72 + 10, p=0.028), migration (average cell count of A549 347 + 41vs190 + 8, p=0.029) (NCI-H292 mean cell count 287 + 33vs127 + 21, p=0.045) and invasion (average cell count 197 + 14 + 14.) The model experiment showed that high expression of miR-338 could effectively inhibit the growth of lung xenografts in nude mice (average number of tumor clones 20 + 7vs4 + 2, p=0.004). Third part of miR-338 could inhibit the metastasis of lung cancer by targeting integrin beta 3: 1, bioinformatics analysis of ITGB3 as a miR-338 target gene.2, using Western immunoblotting MiR-338 overexpressed the expression of ITGB3 protein in the lung cancer cell lines A549 and NCI-H292 and the ITGB3 protein in the control cells, and the dual luciferase reporter detection and verification of the miR-338 target gene.4. The data were analyzed using SPSS 13 and expressed in the form of mean standard deviation. The paired sample t test was used to estimate the difference between the two groups. If P0.05, it was considered between the groups. The difference was statistically significant. Results: 1, the expression of ITGB3 protein in the miR-338 overexpressed lung cancer cell lines A549 and NCI-H292 was significantly lower than that of the control cells (A549 1.0vs0.35 + 0.04, p0.001) (NCI-H2921.0vs0.69 + 0.07, p=0.01).2. The results of the double Luciferase Report showed that the luciferase activity of the miR-338 overexpression group was lower than that of the control group. Low (A549 1.0vs0.75 + 0.08, p=0.03) (NCI-H292 1.0vs0.62 + 0.06, p=0.008). Conclusion: 1, in lung cancer cell lines and lung cancer tissues, the expression level of miR-338 is significantly lower than that of normal cells and tissues. The level of miR-338 expression in lung cancer tissues is not related to sex, age, smoking history, tumor size and lymph node metastasis, but with tumor thrombus and swelling. Tumor recurrence and TNM staging. The total 5 year survival rate of low miR-338 expression group was significantly lower than that of high miR-338 expression group.2. The expression level of miR-338 in lung cancer cells in vitro could effectively inhibit the proliferation of lung cancer cells, adhesion, and reduce the migration and invasion of lung cancer cells.3, miR-338 is through the target gene ITGB3 mRNA3 'UTR area, from the target gene. .miR-338 plays a negative role in regulating its expression..ITGB3 is a new target gene for miR-338 lung cancer. It is a potential new target for gene therapy of lung cancer.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 Takahiro Kishikawa;Motoyuki Otsuka;Motoko Ohno;Takeshi Yoshikawa;Akemi Takata;Kazuhiko Koike;;Circulating RNAs as new biomarkers for detecting pancreatic cancer[J];World Journal of Gastroenterology;2015年28期

2 Michael Hollis;Kavitha Nair;Arpita Vyas;Lakshmi Shankar Chaturvedi;Sahil Gambhir;Dinesh Vyas;;Micro RNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity[J];World Journal of Gastroenterology;2015年27期

3 Pooja Joshi;Justin Middleton;Young-Jun Jeon;Michela Garofalo;;MicroRNAs in lung cancer[J];World Journal of Methodology;2014年02期

，

本文編號(hào)：1806908