本文選題：miR-339 + VEGF　； 參考：《鄭州大學(xué)》2016年博士論文

【摘要】：背景和目的肺癌是目前是全世界腫瘤性疾病死亡率的主要原因,每年可造成多于150萬(wàn)人死亡。目前多數(shù)肺癌患者明確診斷時(shí)已是晚期,臨床癥狀不明顯、早期診斷困難,組織學(xué)亞型不同、對(duì)腫瘤生物學(xué)特征的認(rèn)識(shí)不足導(dǎo)致了肺癌的預(yù)后不良及高死亡率。雖然新的分子靶向治療對(duì)于某些類(lèi)型的肺癌的療效表現(xiàn)出非�？捎^的前景,但目前還沒(méi)有適用于大規(guī)模的肺癌病人的靶向治療�？傮w來(lái)說(shuō),肺癌的總體生存率依然不容樂(lè)觀,很多患者明確診斷后生存期僅僅短短數(shù)月。因此,尋找新型肺癌診斷相關(guān)的腫瘤標(biāo)記物或新的治療策略對(duì)于肺癌的控制顯得至關(guān)重要。miRNA是一段大約由19到25個(gè)核苷酸組成的非編碼小RNA,通過(guò)對(duì)其靶m RNA的翻譯抑制或者降解在動(dòng)植物體內(nèi)發(fā)揮重要的調(diào)節(jié)作用。miRNA是多細(xì)胞生物體內(nèi)眾多基因調(diào)控分子的重要組成部分之一,同時(shí)很可能影響著許多蛋白編碼基因的表達(dá)輸出。miRNA按照其在腫瘤的發(fā)生發(fā)展中的調(diào)控作用可分為致癌miRNA和抑癌miRNA,調(diào)控癌細(xì)胞的增殖、侵襲、凋亡及血管生成情況。miRNA的表達(dá)模式可能與肺癌亞型中臨床病理特征有關(guān),提示了miRNA作為生物標(biāo)志物在腫瘤起源、組織學(xué)類(lèi)型、侵襲性和化學(xué)敏感性等分型中的應(yīng)用潛力�？偟膩�(lái)說(shuō),涉及肺癌的miRNA范圍廣泛,let-7家族、miR-34、miR-200、miR-126等miRNAs在肺癌中的作用已被廣泛研究。通過(guò)查閱相關(guān)文獻(xiàn)及搜索miRBase數(shù)據(jù)庫(kù),發(fā)現(xiàn)miR-339在甲狀腺癌、肺癌、卵巢癌、胃癌等多種腫瘤生長(zhǎng)及侵襲中起到負(fù)向調(diào)控作用。miR-339如何調(diào)控腫瘤的生物學(xué)行為,其具體作用機(jī)制尚未闡明,且miR-339在肺癌尤其是臨床肺癌組織中的表達(dá)情況亦較少研究。目前多數(shù)研究者認(rèn)為腫瘤的生長(zhǎng)必須依靠新生血管的生成來(lái)提供其足夠的氧氣和營(yíng)養(yǎng)物質(zhì),因此以抗腫瘤血管為主的治療成為腫瘤臨床治療的熱點(diǎn),血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor,VEGF)被認(rèn)為可作用于血管內(nèi)皮細(xì)胞,誘導(dǎo)體內(nèi)新生血管生成。抑制VEGF的作用也成為了抑制腫瘤生長(zhǎng)的臨床研究基礎(chǔ)。當(dāng)VEGF與特異性的VEGF受體結(jié)合后,會(huì)發(fā)生一系列的生物效應(yīng),能促進(jìn)血管內(nèi)皮細(xì)胞增殖誘導(dǎo)新血管的生成;增加血管通透性;改變血管內(nèi)皮細(xì)胞的基因及其表達(dá),利于新血管的形成。本研究通過(guò)miRNA的靶基因預(yù)測(cè)數(shù)據(jù)庫(kù)對(duì)miR-339的靶基因進(jìn)行預(yù)測(cè),對(duì)3種靶基因預(yù)測(cè)數(shù)據(jù)庫(kù)所預(yù)測(cè)的靶基因交集進(jìn)行功能分析,最終篩選出VEGF作為miR-339的靶基因進(jìn)行研究。本課題分為三個(gè)部分:第一部分通過(guò)qRT-PCR及Western blot方法分析41例肺腺癌組織中miR-339和VEGF的表達(dá)水平;第二部分采用慢病毒載體技術(shù),建立穩(wěn)定高表達(dá)miR-339的肺腺癌A549細(xì)胞株,研究體內(nèi)外上調(diào)miR-339表達(dá)對(duì)肺腺癌A549細(xì)胞增殖、侵襲、化療敏感性及血管生成的影響;第三部分通過(guò)雙熒光素酶報(bào)告實(shí)驗(yàn)及Restore實(shí)驗(yàn)進(jìn)一步研究miR-339對(duì)VEGF轉(zhuǎn)錄后的調(diào)控機(jī)制。第一部分41例肺腺癌組織中miR-339和VEGF的表達(dá)水平分析方法1.收集41例肺腺癌組織與相應(yīng)配對(duì)的癌旁正常組織標(biāo)本。2.運(yùn)用qRT-PCR技術(shù)檢測(cè)41例標(biāo)本中miR-339及VEGFmRNA的表達(dá)水平,Spearman相關(guān)分析對(duì)二者的相關(guān)性進(jìn)行分析;Western blot方法檢測(cè)41例標(biāo)本中VEGF蛋白表達(dá)水平。3.分析miR-339與VEGFm RNA在不同年齡、性別、淋巴結(jié)轉(zhuǎn)移情況、分化程度、TNM分期病例之間是否存在差異。4.統(tǒng)計(jì)學(xué)方法:本研究數(shù)據(jù)應(yīng)用SPSS 21.0軟件進(jìn)行統(tǒng)計(jì)分析,符合正態(tài)分布的數(shù)據(jù)以表示;單因素方差分析用于同時(shí)具備正態(tài)性及方差齊性數(shù)據(jù)的多項(xiàng)指標(biāo)間的比較,LSD-t檢驗(yàn)用于多組數(shù)據(jù)的兩兩比較;t檢驗(yàn)用于兩獨(dú)立樣本計(jì)量資料的比較,配對(duì)t檢驗(yàn)用于兩配對(duì)樣本計(jì)量資料的比較;Spearman相關(guān)分析用于兩組數(shù)據(jù)資料的相關(guān)性分析,檢驗(yàn)水準(zhǔn)α=0.05。結(jié)果1.miR-339在肺癌組織中的表達(dá)約為癌旁正常組織的1/3,而VEGFm RNA的表達(dá)水平是癌旁正常組織的3倍,二者的表達(dá)水平之間存在負(fù)相關(guān)性(r=-0.419,P=0.006)。2.miR-339及VEGFmRNA在不同TNM分期及淋巴結(jié)轉(zhuǎn)移情況的肺腺癌組織中表達(dá)水平差異有統(tǒng)計(jì)學(xué)意義(P0.05)。第二部分上調(diào)miR-339表達(dá)對(duì)肺腺癌A549細(xì)胞增殖、侵襲、化療敏感性及血管生成的影響方法1.制備和包裝miR-339及無(wú)關(guān)序列慢病毒表達(dá)載體,感染肺腺癌A549細(xì)胞,建立穩(wěn)定高表達(dá)miR-339的肺腺癌A549細(xì)胞株,實(shí)驗(yàn)分miR-339組,NC組,Blank組。2.qRT-PCR檢測(cè)三組細(xì)胞miR-339及VEGFmRNA表達(dá),Western blot檢測(cè)VEGF蛋白及侵襲相關(guān)蛋白MMP2、MMP9表達(dá)。3.CCK-8、克隆形成實(shí)驗(yàn)檢測(cè)三組細(xì)胞的增殖能力。4.Transwell小室檢測(cè)三組細(xì)胞的侵襲能力。5.CCK-8檢測(cè)不同濃度順鉑作用下三組細(xì)胞的增殖能力。6.建立裸鼠移植瘤模型,應(yīng)用小動(dòng)物活體成像儀檢測(cè)三組裸鼠瘤體的增殖情況。7.小動(dòng)物活體成像儀檢測(cè)順鉑作用下裸鼠瘤體的增殖情況。8.免疫組化技術(shù)檢測(cè)移植瘤標(biāo)本的微血管密度變化。9.采用SPSS 21.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析,檢驗(yàn)水準(zhǔn)α=0.05。結(jié)果1.成功制備miR-339及無(wú)關(guān)序列重組慢病毒載體,二者重組慢病毒滴度分別為1.6×108TU/m L及2.2×108 TU/m L。miR-339在miR-339組表達(dá)水平明顯高于NC組及Blank組(P0.05)。2.miR-339組VEGFm RNA表達(dá)水平明顯低于NC組及Blank組,Westren blot顯示miR-339組VEGF、MMP2、MMP9蛋白表達(dá)較NC組、Blank組明顯降低(P0.05)。3.CCK-8結(jié)果顯示,miR-339組細(xì)胞的吸光度值在24h,48h,72h較Blank組及NC組明顯降低,且隨時(shí)間延長(zhǎng),其差異呈增大趨勢(shì)(P0.05)。4.克隆形成實(shí)驗(yàn)顯示,miR-339組克隆形成數(shù)較NC組及Blank組明顯減少(P0.05)。5.Transwell小室結(jié)果顯示,miR-339組細(xì)胞transwell穿膜細(xì)胞數(shù)較NC組及Blank組明顯減少(P0.05),Blank組及NC組之間穿膜細(xì)胞數(shù)無(wú)明顯差異(P0.05)。6.CCK-8檢測(cè)0μg/m L,4μg/m L,8μg/m L,12μg/m L,16μg/m L,20μg/m L濃度順鉑作用24小時(shí)的吸光度值,結(jié)果顯示,三組細(xì)胞的細(xì)胞活力隨順鉑濃度升高而降低(P0.05);miR-339組細(xì)胞在順鉑作用下細(xì)胞活力降低程度較NC組及Blank組細(xì)胞更大,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。7.小動(dòng)物活體成像系統(tǒng)檢測(cè)裸鼠移植瘤體內(nèi)增殖結(jié)果顯示,從第2周起,miR-339組裸鼠移植瘤熒光信號(hào)較Blank組及NC組均明顯降低(P0.05),且隨時(shí)間延長(zhǎng),miR-339組瘤體與Blank組及NC組熒光信號(hào)差異愈加顯著(P0.05)。8.順鉑作用下miR-339組裸鼠移植瘤熒光信號(hào)較Blank組及NC組均明顯降低(P0.05),三組裸鼠移植瘤順鉑組的熒光信號(hào)均較無(wú)順鉑組降低(P0.05),其中miR-339組在順鉑作用下熒光信號(hào)下降程度較Blank組及NC組更加顯著(P0.05)。9.miR-339組裸鼠移植瘤標(biāo)本微血管密度較Blank組及NC組相比均明顯降低(P0.05)。第三部分miR-339對(duì)VEGF轉(zhuǎn)錄后調(diào)控機(jī)理的研究方法1.運(yùn)用miRNA的靶基因預(yù)測(cè)數(shù)據(jù)庫(kù)對(duì)miR-339的靶基因進(jìn)行預(yù)測(cè)。2.構(gòu)建pmir GLO-Wt(野生型)及pmir GLO-Mt(seed region突變型)熒光素酶雙報(bào)告基因載體,分組轉(zhuǎn)染A549細(xì)胞,雙報(bào)告基因驗(yàn)證miR-339的靶基因。3.構(gòu)建不含3'UTR VEGF的pcDNA3.1-VEGF表達(dá)載體,分別單獨(dú)轉(zhuǎn)染、與miR-339mimics共轉(zhuǎn)染A549細(xì)胞,Western blot方法檢測(cè)各組細(xì)胞VEGF表達(dá)情況,Transwell小室檢測(cè)各組細(xì)胞侵襲能力,restore方法分析miR-339對(duì)VEGF的調(diào)控機(jī)制。4.采用SPSS 21.0統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析。結(jié)果1.通過(guò)數(shù)據(jù)庫(kù)預(yù)測(cè)VEGF可能為miRNA的靶基因,二者之間存在互補(bǔ)配對(duì)的“seed region”區(qū),成功構(gòu)建pmir GLO-Wt及pmir GLO-Mt報(bào)告基因重組載體,并轉(zhuǎn)染A549細(xì)胞。2.雙熒光素酶報(bào)告實(shí)驗(yàn)顯示miR-339mimics、pmirGLO-Wt共轉(zhuǎn)染組細(xì)胞的熒光素酶活性較miR-339scramble、pmir GLO-Wt共轉(zhuǎn)染組及miR-339mimics、pmir GLO-Mt共轉(zhuǎn)染組明顯降低,miR-339可作用于VEGF 3’UTR區(qū)并產(chǎn)生負(fù)調(diào)控作用使其表達(dá)降低。3.成功構(gòu)建不含VEGF 3’UTR的pcDNA3.1-VEGF重組表達(dá)載體,Restore實(shí)驗(yàn)顯示,將不含VEGF 3’UTR的pc DNA3.1-VEGF重組載體轉(zhuǎn)染至A549細(xì)胞后,可回復(fù)上調(diào)miR-339對(duì)VEGF蛋白表達(dá)的抑制作用及miR-339對(duì)A549細(xì)胞的侵襲抑制作用。結(jié)論1.miR-339在肺腺癌組織中呈低表達(dá),VEGF在肺癌組織中呈高表達(dá),二者之間存在負(fù)相關(guān),miR-339及VEGF表達(dá)水平在不同淋巴結(jié)轉(zhuǎn)移情況及不同TNM分期之間存在差異。2.體外上調(diào)miR-339表達(dá)可降低肺腺癌A549細(xì)胞的增殖及侵襲能力,增加細(xì)胞對(duì)順鉑的敏感性,動(dòng)物實(shí)驗(yàn)表明上調(diào)miR-339表達(dá)可抑制裸鼠移植瘤的增殖,增加其對(duì)順鉑的敏感性,降低瘤組織微血管密度。3.miR-339通過(guò)作用于VEGF的3’UTR區(qū)對(duì)其表達(dá)產(chǎn)生負(fù)調(diào)控作用。
[Abstract]:Background and objective lung cancer is the main cause of mortality in all the world's Oncology, which can cause more than 1 million 500 thousand deaths a year. At present, most patients with lung cancer are clearly diagnosed at the present time, the clinical symptoms are not obvious, the early diagnosis is difficult, the histologic subtypes are different, and the lack of understanding of the biological characteristics of the tumor leads to the prognosis of lung cancer. Poor and high mortality. Although new molecular targeting therapy has shown great prospects for the efficacy of some types of lung cancer, it is not yet suitable for targeted therapy for large scale lung cancer patients. Overall, the overall survival rate of lung cancer is still not optimistic, and many patients have a clear diagnosis of only a few months after the diagnosis. Therefore, looking for tumor markers related to new lung cancer diagnosis or new treatment strategies is important for the control of lung cancer..miRNA is a non coded small RNA, which is composed of approximately 19 to 25 nucleotides, and the.MiRNA is a multicell organism by inhibiting or degradation of the target m RNA. One of the most important components of a number of gene regulatory molecules in the body is likely to affect the expression of a number of protein encoding genes, which can be divided into carcinogenic miRNA and tumor suppressor miRNA in accordance with its regulatory role in the development of tumor, and the expression pattern of.MiRNA, which regulates the proliferation, invasion, apoptosis and angiogenesis of cancer cells, may be regulated. It is associated with the clinicopathological features of lung cancer subtypes, suggesting the potential application of miRNA as a biomarker in tumor origin, histologic type, invasive and chemosensitivity isoforms. Generally, the miRNA range involving lung cancer is wide, and the role of miRNAs in the let-7 family, miR-34, miR-200, miR-126 and other miRNAs in lung cancer has been widely studied. After consulting related literature and searching for miRBase database, it is found that miR-339 plays a negative regulatory role in the growth and invasion of thyroid cancer, lung cancer, ovarian cancer and gastric cancer, and how.MiR-339 regulates the biological behavior of the tumor. Its specific mechanism has not been elucidated, and the expression of miR-339 in lung cancer, especially in lung cancer tissues At present, most researchers believe that the growth of tumor must rely on the formation of new blood vessels to provide enough oxygen and nutrients. Therefore, the antitumor vascular therapy has become a hot spot in the clinical treatment of tumor. Vascular endothelial growth factor (VEGF) is considered to be a function of blood vessels. Endothelial cells, which induce neovascularization in the body, inhibit the role of VEGF as a basis for the inhibition of tumor growth. When VEGF is combined with a specific VEGF receptor, a series of biological effects will occur, which can promote the proliferation of vascular endothelial cells to induce the generation of new blood vessels, increase vascular permeability, and change vascular endothelial cells. Gene and its expression are beneficial to the formation of new blood vessels. In this study, the target gene of the target gene of miR-339 was predicted by the target gene prediction database of miRNA, and the target gene intersection predicted by the 3 target gene prediction database was analyzed. Finally, the target gene of VEGF was selected as the target gene of miR-339. The subject was divided into three parts: the first part The expression level of miR-339 and VEGF in 41 cases of lung adenocarcinoma was analyzed by qRT-PCR and Western blot. The second part of the lung adenocarcinoma A549 cell line with high expression of miR-339 was established by lentivirus vector technology, and the effects of the up regulation of miR-339 expression on the A549 cell proliferation, invasion, chemosensitivity and angiogenesis of lung adenocarcinoma in vivo and in vivo were studied. The third part, through the double Luciferase Report experiment and the Restore experiment, further studies the regulatory mechanism of miR-339 after VEGF transcription. Part 1: analysis of the expression level of miR-339 and VEGF in 41 cases of lung adenocarcinoma 1. to collect 41 cases of lung adenocarcinoma tissue and the corresponding paired normal tissue specimens of the paracancerous tissue,.2. using qRT-PCR technique to detect 41 cases. The expression level of miR-339 and VEGFmRNA in this study, the correlation of Spearman correlation analysis to the two, Western blot method was used to detect the VEGF protein expression level.3. analysis of miR-339 and VEGFm RNA in different age, sex, lymph node metastasis, differentiation degree, TNM staging between the existence of.4. statistical methods: SPSS 21 software is used for statistical analysis in accordance with the data of normal distribution; single factor variance analysis is used for the comparison of multiple indexes with normal and variance homogeneity data. The LSD-t test is used for 22 comparison of multiple groups of data; t test is used for comparison of two independent sample data and paired t test For comparison of two paired sample data, Spearman correlation analysis was used for correlation analysis of two groups of data. The expression of 1.miR-339 in lung cancer tissue was approximately 1/3 in the normal tissues adjacent to cancer, while the expression level of VEGFm RNA was 3 times as high as that of normal tissue adjacent to the cancer, and there was a negative correlation between the level of expression of the two groups. The expression level of r=-0.419, P=0.006.2.miR-339 and VEGFmRNA in the lung adenocarcinoma tissues of different TNM staging and lymph node metastasis was statistically significant (P0.05). Second part up regulation of miR-339 expression on the proliferation, invasion, chemosensitivity and angiogenesis of A549 cells of lung adenocarcinoma 1. preparation and packaging miR-339 and unrelated order The expression vector of lentivirus was used to infect A549 cells of lung adenocarcinoma and to establish a A549 cell line with high expression of miR-339 in lung adenocarcinoma. The expression of miR-339 and VEGFmRNA in three groups was detected in group miR-339, NC and Blank, and Western blot was used to detect the VEGF protein and invasion related protein. Cell proliferation ability.4.Transwell cell detection of three groups of cell invasiveness.5.CCK-8 detection of the proliferation ability of three groups of cells under the action of cisplatin and.6. to establish a nude mouse transplanted tumor model. The proliferation of three groups of nude mice was detected by small animal living imaging apparatus and.7. small animal living body imager was used to detect nude mice under cisplatin The proliferation of.8. immunohistochemical technique was used to detect the microvascular density change of the transplanted tumor specimens..9. was analyzed by SPSS 21 software. The level of alpha =0.05. results 1. was tested to produce miR-339 and unrelated recombinant lentivirus vector successfully. The two of the recombinant lentivirus titers were 1.6 * 108TU/m L and 2.2 x 108 TU/m L.miR-339 respectively in miR-33. The expression level of 9 groups was significantly higher than that of group NC and group Blank (P0.05).2.miR-339 group VEGFm RNA expression level was significantly lower than that of NC group and Blank group. Westren blot showed miR-339 VEGF. The difference showed an increasing trend (P0.05).4. clone formation experiment showed that the number of clone formation in miR-339 group was significantly lower than that of NC group and Blank group (P0.05).5.Transwell chamber results showed that the number of Transwell transmembrane cells in miR-339 group was lower than that of NC and Blank group (P0.05), and the number of membrane cells between the group and the group was not clear. The significant difference (P0.05).6.CCK-8 detected 0 mu g/m L, 4 mu g/m L, 8 mu g/m L, 12 micron L, 16 micron g/m L, and 20 micron concentration of cisplatin for 24 hours. The results showed that the cell viability in the three groups decreased with the increase of cisplatin concentration. P0.05.7. small animal living imaging system detected the proliferation of xenograft in nude mice. From second weeks, the fluorescence signal of miR-339 group was significantly lower than that of group Blank and NC group (P0.05), and the difference of fluorescence signal between miR-339 group and Blank group and NC group was more significant (P0.05).8. along with time. The fluorescence signal of miR-339 group nude mice was significantly lower than that of group Blank and NC group (P0.05). The fluorescence signal of cisplatin group in three groups of nude mice was lower than that in non cisplatin group (P0.05). The decrease of fluorescence signal in miR-339 group was more significant than that in Blank group and NC group (P0.05).9.miR-339 group nude mice transplantation tumor specimen The microvascular density was significantly lower than that of the Blank group and the NC group (P0.05). Third a study on the mechanism of post transcriptional regulation of VEGF. 1. using the target gene prediction database of miRNA to predict the target gene of miR-339 for the construction of pmir GLO-Wt (wild type) and pmir GLO-Mt (mutant type) luciferase double reporter gene carrier A549 cells were transfected into groups, and the double reporter gene validated the target gene.3. of miR-339 to construct pcDNA3.1-VEGF expression vector without 3'UTR VEGF, and transfected separately, respectively, and co transfected with A549 cells with miR-339mimics, Western blot method was used to detect the VEGF expression of each cell, and the Transwell chamber was used to detect the invasion ability of each cell. The regulatory mechanism of VEGF.4. uses SPSS 21 statistical software for data analysis. Results 1. it is predicted that VEGF may be the target gene of miRNA through the database, and the complementary pairing "seed region" region exists between the two and the recombinant vector of pmir GLO-Wt and pmir GLO-Mt reporter gene is successfully constructed, and the experiment of transfection of A549 cells with double Luciferase Report is shown. The luciferase activity of miR-339mimics, pmirGLO-Wt co transfected group was significantly lower than that of miR-339scramble, pmir GLO-Wt co transfection group and miR-339mimics, pmir GLO-Mt co transfection group was significantly reduced, miR-339 could act on VEGF 3 'UTR region and produce negative regulatory action to reduce the recombinant expression of.3. successfully constructed without 3' Restore experiments showed that the transfection of PC DNA3.1-VEGF recombinant vector without VEGF 3 'UTR to A549 cells could restore the inhibitory effect of miR-339 on the expression of VEGF protein and the inhibitory effect of miR-339 on A549 cells. Conclusion 1.miR-339 is expressed in lung adenocarcinoma tissue, and VEGF is highly expressed in lung cancer tissues, and between the two groups. There was a negative correlation. The expression level of miR-339 and VEGF in different lymph node metastases and different TNM stages was different between.2. and miR-339 expression in vitro. The expression of miR-339 could reduce the proliferation and invasion ability of A549 cells in lung adenocarcinoma and increase the sensitivity of cell to cisplatin. Animal experiments showed that up regulation of miR-339 expression could inhibit the proliferation of nude mice. In addition, its sensitivity to cisplatin decreased the microvessel density of tumor tissues..3.miR-339 negatively regulates the expression of VEGF through 3 'UTR region.
【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(lèi)號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前4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 Xun Yang;Bei-Bei Chen;Ming-Hua Zhang;Xin-Rong Wang;;MicroRNA-126 inhibits the proliferation of lung cancer cell line A549[J];Asian Pacific Journal of Tropical Medicine;2015年03期

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

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