本文選題：甲狀腺乳頭狀癌 + miR-29a��； 參考：《吉林大學(xué)》2016年博士論文

【摘要】：甲狀腺癌是最常見的內(nèi)分泌系統(tǒng)惡性腫瘤,占全部內(nèi)分泌惡性腫瘤總數(shù)的94.5%,其發(fā)病率在頭頸部惡性腫瘤中居首位。在過去的幾十年間,其發(fā)病率一直呈穩(wěn)步上升趨勢。甲狀腺乳頭狀癌(PTC)是一種公認(rèn)的分化較好的惡性腫瘤,也是最常見的甲狀腺惡性腫瘤,約占甲狀腺癌總數(shù)的80%~90%。多數(shù)PTC患者預(yù)后良好,但總體復(fù)發(fā)率仍可高達(dá)35%,因?yàn)槟壳暗氖侄芜�不能準(zhǔn)確地預(yù)測其臨床轉(zhuǎn)歸和生物學(xué)行為。因此,我們迫切的需要了解甲狀腺乳頭狀癌發(fā)生發(fā)展的分子機(jī)制,并且找到一系列嶄新的有助于PTC的及時(shí)診斷、判斷預(yù)后和有效治療的從宏觀到微觀的診療思路。微小RNA(mi RNAs)是一類非編碼小RNA,長度約在19~25個(gè)核苷酸�？膳c信使RNA(m RNAs)的3’非編碼區(qū)(3’-UTR)互補(bǔ)結(jié)合,在轉(zhuǎn)錄水平或轉(zhuǎn)錄后水平調(diào)節(jié)基因的表達(dá)。目前研究發(fā)現(xiàn)mi RNAs可能可以調(diào)節(jié)上千種人類基因的轉(zhuǎn)錄與表達(dá),并且,越來越多的證據(jù)表明,mi RNAs還可以調(diào)節(jié)許多基礎(chǔ)生理過程,如細(xì)胞的分化、增殖和存活,以及細(xì)胞凋亡、遷移和侵襲等。因?yàn)閙i RNAs可以參與調(diào)節(jié)細(xì)胞增殖、分化與凋亡,所以認(rèn)為它與癌癥的發(fā)生與發(fā)展有著密切關(guān)系。進(jìn)而,分析mi RNAs及其靶基因不但把我們對(duì)腫瘤發(fā)生發(fā)展的認(rèn)識(shí)引入到了一個(gè)獨(dú)特而嶄新的視角,而且為PTC的診斷和治療提供了新的切入點(diǎn)。mi R-29a是mi R-29s家族中的一員,這是一個(gè)保守的mi RNA家族,mi R-29s在一些癌癥中表達(dá)減少,如胃癌、胰腺癌和前列腺癌等;恰恰相反,mi R-29s在另一些癌癥中的表達(dá)是上升的,如乳腺癌、鼻咽癌、神經(jīng)膠質(zhì)瘤和急性髓性白血病等。這些研究表明,mi R-29a可能在不同的癌癥中發(fā)揮著促進(jìn)或抑制腫瘤發(fā)生發(fā)展的作用。然而,它在PTC中的臨床意義、作用和潛在分子機(jī)制仍不十分清楚,在本研究中,我們分析了mi R-29a的表達(dá)與PTC患者臨床病理特征之間的關(guān)系,并且通過一系列體外和體內(nèi)實(shí)驗(yàn)來研究mi R-29a在PTC中發(fā)揮的作用和潛在的機(jī)制。目的:明確mi R-29a在甲狀腺乳頭狀癌發(fā)生發(fā)展中的作用及機(jī)制方法:1.研究mi R-29a在PTC中的表達(dá)水平及其在增殖和遷移中的作用和機(jī)制(1)本實(shí)驗(yàn)通過q RT-PCR對(duì)30組PTC腫瘤患者組織標(biāo)本及其鄰近的正常組織中的mi R-29a的表達(dá)進(jìn)行的分析,為了進(jìn)一步研究mi R-29a表達(dá)水平在PTC患者中的臨床病理學(xué)意義,我們選取中位數(shù)(0.59)為分界點(diǎn),將30個(gè)PTC標(biāo)本分為mi R-29a相對(duì)低水平組(0.59,14 cases)和mi R-29a相對(duì)高水平組(0.59,16 cases),然后將mi R-29a的表達(dá)與臨床病理學(xué)參數(shù)使用卡方檢驗(yàn)分析。(2)為了闡明mi R-29a在PTC中的生物學(xué)功能,我們將mi R-29a模擬物轉(zhuǎn)染到K1細(xì)胞系中,并獲得穩(wěn)定表達(dá)mi R-29a的K1細(xì)胞系。經(jīng)過q RT-PCR證實(shí)mi R-29a的表達(dá)水平在K1細(xì)胞系中確實(shí)增加,然后將mi R-29a模擬物和mi R-Ctrl分別轉(zhuǎn)染到K1細(xì)胞系中用以檢測細(xì)胞增殖、細(xì)胞周期和細(xì)胞凋亡。(3)通過傷口愈合實(shí)驗(yàn)和腫瘤細(xì)胞侵襲實(shí)驗(yàn)來研究mi R-29a調(diào)節(jié)PTC細(xì)胞侵襲和遷移的作用。2.mi R-29a通過調(diào)節(jié)AKT3而抑制PTC生長的機(jī)制研究(1)我們使用生物學(xué)信息數(shù)據(jù)庫如Target Scan,mi Randa和Pic Tar對(duì)mi R-29a的潛在靶基因進(jìn)行預(yù)測,AKT3被鎖定為研究目標(biāo),因?yàn)樗赑I3K/AKT信號(hào)通路中發(fā)揮重要作用并且涉及多種細(xì)胞功能。為了驗(yàn)證AKT3是否是mi R-29a在PTC中的直接目標(biāo),一個(gè)人類AKT3 3’UTR包含mi R-29a結(jié)合位點(diǎn)的片段或克隆了突變位點(diǎn)的PGL3載體,連同mi R-29a模擬物或mi R-Ctrl共轉(zhuǎn)染進(jìn)K1細(xì)胞,并孵育48h,然后檢測熒光素酶的活性。通過q RT-PCR和western blotting實(shí)驗(yàn)分別從m RNA水平和蛋白質(zhì)水平檢測mi R-29a過表達(dá)對(duì)K1細(xì)胞中的AKT3表達(dá)水平的影響。(2)已經(jīng)明確AKT3是mi R-29a的靶基因,我們繼續(xù)使用q RT-PCR研究AKT3在PTC組織及其臨近正常組織中的表達(dá)量。(3)為了進(jìn)一步探究AKT3在PTC中的生物學(xué)作用,我們將si-AKT3和si-Ctrl分別轉(zhuǎn)染進(jìn)K1細(xì)胞,使用q RT-PCR和western blot驗(yàn)證AKT3的敲除效率。使用si-AKT3沉默AKT3基因后,繼續(xù)使用MTT比色法檢測細(xì)胞增殖、流式細(xì)胞術(shù)檢測細(xì)胞凋亡、傷口愈合實(shí)驗(yàn)檢測細(xì)胞遷移和腫瘤細(xì)胞侵襲實(shí)驗(yàn)檢測細(xì)胞侵襲。(4)為了進(jìn)一步研究AKT3針對(duì)于mi R-29a的相關(guān)功能,我們設(shè)計(jì)了一系列實(shí)驗(yàn),對(duì)于當(dāng)AKT3過表達(dá)時(shí),是否會(huì)對(duì)mi R-29a在PTC細(xì)胞增殖、凋亡、遷移和侵襲等作用產(chǎn)生影響進(jìn)行評(píng)估。為此,AKT3過表達(dá)質(zhì)粒與mi R-29a模擬物或mi R-Ctrl一同轉(zhuǎn)染到K1細(xì)胞中。接著使用MTT比色法檢測細(xì)胞增殖、流式細(xì)胞術(shù)檢測細(xì)胞凋亡、傷口愈合實(shí)驗(yàn)檢測細(xì)胞遷移和腫瘤細(xì)胞侵襲實(shí)驗(yàn)檢測細(xì)胞侵襲能力。3.mi R-29a在體內(nèi)抑制PTC生長的實(shí)驗(yàn)研究體外實(shí)驗(yàn)顯示miR-29a有抑制腫瘤生長的作用,我們進(jìn)而對(duì)它的作用在體內(nèi)進(jìn)行了評(píng)估。為了這一目的,我們將穩(wěn)定表達(dá)mi R-29a或mi R-Ctrl的K1細(xì)胞種植到裸鼠皮下,使其形成腫瘤。在注射后30天,將動(dòng)物處死,剝?nèi)∧[瘤組織。觀察并測量兩組腫瘤的大小和重量。此外,我們還通過q RT-PCR測定了mi R-29a和AKT3在腫瘤組織中的表達(dá),接著通過q RT-PCR和western blotting實(shí)驗(yàn)分別從m RNA水平和蛋白質(zhì)水平測定AKT3的表達(dá)水平。結(jié)果:1.mi R-29a在PTC中的表達(dá)水平及其在增殖和遷移中的作用及機(jī)制(1)mi R-29a在人PTC組織中表達(dá)下調(diào)PTC組織中的mi R-29a的相對(duì)表達(dá)量要明顯低于其鄰近正常組織(P0.01)。我們選取中位數(shù)(0.59)為分界點(diǎn),將30個(gè)PTC標(biāo)本分為mi R-29a相對(duì)低水平組(0.59,14 cases)和mi R-29a相對(duì)高水平組(0.59,16 cases),然后將mi R-29a的表達(dá)與臨床病理學(xué)參數(shù)使用卡方檢驗(yàn)分析。分析顯示mi R-29a的表達(dá)與年齡和性別的相關(guān)性沒有統(tǒng)計(jì)學(xué)意義,同時(shí),mi R-29a的水平與TNM分期(P0.01)、腫瘤大小(P0.01)和淋巴結(jié)轉(zhuǎn)移(P0.01)呈負(fù)相關(guān)趨勢。(2)mi R-29a可抑制PTC細(xì)胞增殖并誘導(dǎo)凋亡經(jīng)過q RT-PCR證實(shí)mi R-29a的表達(dá)水平在K1細(xì)胞系中確實(shí)增加(p0.01),MTT比色法顯示mi R-29a可顯著抑制K1細(xì)胞的增殖,與轉(zhuǎn)染了mi R-Ctrl組對(duì)比,在48h時(shí)P0.05,而72h時(shí)P0.01,具有統(tǒng)計(jì)學(xué)意義。細(xì)胞周期分析顯示,與轉(zhuǎn)染了mi R-Ctrl組對(duì)比,恢復(fù)了mi R-29a的K1細(xì)胞中的S期的比例降低(P0.05),而G0/G1期比例顯著升高(P0.01)。細(xì)胞凋亡實(shí)驗(yàn)顯示在K1細(xì)胞系中轉(zhuǎn)染了mi R-29a模擬物可明顯促進(jìn)細(xì)胞凋亡,與轉(zhuǎn)染mi R-Ctrl組對(duì)比,P0.01。(3)miR-29a可抑制PTC細(xì)胞侵襲和遷移與mi R-Ctrl組比較,增加miR-29a的表達(dá)水平可顯著抑制K1細(xì)胞的侵襲和轉(zhuǎn)移的能力(p0.01)。2.mi R-29a通過調(diào)節(jié)AKT3而抑制PTC生長的機(jī)制研究(1)AKT3是mi R-29a的直接靶基因miR-29a過表達(dá)明顯抑制了野生型AKT3位點(diǎn)的熒光素酶活性,但是突變型AKT3位點(diǎn)的熒光素酶活性并沒有改變。這表明AKT3是mi R-29a的直接靶基因。然后通過q RT-PCR和western blotting實(shí)驗(yàn)證實(shí)mi R-29a過表達(dá)可徹底地抑制K1細(xì)胞中的AKT3表達(dá)水平,無論是從m RNA水平還是從蛋白質(zhì)水平。另外,我們還發(fā)現(xiàn),過表達(dá)的mi R-29a可抑制磷酸化AKT(p-AKT)的表達(dá),這提示mi R-29a可以抑制PI3K/AKT信號(hào)轉(zhuǎn)導(dǎo)通路的激活。以上結(jié)果表明,mi R-29a可直接與AKT3結(jié)合并抑制其表達(dá)。(2)在PTC組織中mi R-29a的表達(dá)與AKT3的表達(dá)是負(fù)性相關(guān)的與周圍臨近正常組織相比,AKT3的m RNA表達(dá)量在PTC組織中是升高的(P0.01)。并且,在PTC組織中,AKT3的表達(dá)量與mi R-29a的表達(dá)量是負(fù)性相關(guān)的(P0.01)。(3)下調(diào)AKT3的表達(dá)可模擬mi R-29a過表達(dá)的效果使用si-AKT3下調(diào)K1細(xì)胞系中的AKT3的表達(dá)可抑制細(xì)胞增殖并且誘導(dǎo)細(xì)胞凋亡,同時(shí)也可以抑制腫瘤細(xì)胞的遷徙和侵襲能力。換言之,減少AKT3的表達(dá)可模擬mi R-29a抑制腫瘤的效果。(4)AKT3過表達(dá)可逆轉(zhuǎn)mi R-29a的作用AKT3過表達(dá)質(zhì)�？梢栽趍 RNA水平以及蛋白質(zhì)水平上增加AKT3的表達(dá)。AKT3在K1細(xì)胞中過表達(dá)可以促進(jìn)腫瘤細(xì)胞增殖、遷移和侵襲、抑制細(xì)胞凋亡,即AKT3過表達(dá)可逆轉(zhuǎn)mi R-29a抑制腫瘤的作用。3.mi R-29a在體內(nèi)抑制PTC生長與注射K1/miR-Ctrl組對(duì)比,注射K1/miR-29a組的腫瘤無論是在大小還是重量上都要明顯減少(P0.01)。此外,腫瘤組織中的mi R-29a的表達(dá)水平要明顯升高(P0.01),然而,AKT3的表達(dá)水平卻顯著地下降,無論是在m RNA水平(P0.01)還是蛋白質(zhì)水平。結(jié)論:1.miR-29a的表達(dá)水平在PTC組織中是減少的,并且其表達(dá)水平與腫瘤的大小、TNM分期和是否有淋巴結(jié)轉(zhuǎn)移有著密切的關(guān)系。2.mi R-29a過表達(dá)可顯著抑制PTC細(xì)胞增殖、遷移和侵襲,并且促進(jìn)PTC細(xì)胞凋亡,使細(xì)胞周期停滯在G0/G1期。體內(nèi)實(shí)驗(yàn)證實(shí),mi R-29a過表達(dá)可通過調(diào)節(jié)AKT3降低異種腫瘤移植裸鼠模型中的腫瘤生長。3.在PTC細(xì)胞中,miR-29a可與AKT3的3’非編碼區(qū)直接結(jié)合,過表達(dá)的mi R-29a可顯著抑制AKT3的表達(dá),從而阻止(PI3K)/AKT信號(hào)轉(zhuǎn)導(dǎo)途徑的激活。4.在PTC組織中,AKT3的表達(dá)是增加的,并且其表達(dá)與miR-29a的表達(dá)是呈負(fù)相關(guān)的。使用si RNA降低AKT3的表達(dá)可模擬mi R-29a過表達(dá)的效果,反之,上調(diào)AKT3的表達(dá)可部分逆轉(zhuǎn)mi R-29a抑制腫瘤生長的作用。
[Abstract]:Thyroid carcinoma is the most common malignant tumor of the endocrine system, accounting for 94.5% of the total number of endocrine malignant tumors. The incidence of thyroid cancer is the first in the head and neck malignant tumor. The incidence of thyroid cancer has been steadily increasing in the past several decades. Thyroid papillary carcinoma (PTC) is recognized as a well differentiated malignant tumor, and is the most frequent. Most of the 80%~90%. patients with thyroid malignant tumors, which account for the total number of thyroid cancer, have a good prognosis, but the overall recurrence rate can still be as high as 35%, because the current means can not accurately predict their clinical outcome and biological behavior. Therefore, we urgently need to understand the molecular mechanism of the development of thyroid papillary carcinoma and find out the molecular mechanism of the development of thyroid papillary carcinoma and find out the molecular mechanism of the development of thyroid papillary carcinoma. A new series of new diagnostics that contribute to the timely diagnosis of PTC to judge the prognosis and effective treatment from macro to microcosmic. The small RNA (MI RNAs) is a class of non coded small RNA with a length of about 19~25 nucleotides. The 3 'non coding region (3' -UTR) of the messenger RNA (m RNAs) can be combined with each other to regulate the gene table at the transcriptional level or post transcriptional level. Da. Current research has found that MI RNAs may regulate the transcription and expression of thousands of human genes, and more and more evidence suggests that MI RNAs can also regulate many basic physiological processes, such as cell differentiation, proliferation and survival, and cell apoptosis, migration and invasion, because mi RNAs can participate in regulating cell proliferation, differentiation and withering. It is believed that it is closely related to the occurrence and development of cancer. Then, the analysis of MI RNAs and its target genes not only introduce our understanding of tumor development to a unique and new perspective, but also provide a new entry point for the diagnosis and treatment of PTC,.Mi R-29a is a member of the Mi R-29s family, which is a conservative. The MI RNA family, MI R-29s, is expressed in some cancers, such as gastric cancer, pancreatic cancer, and prostate cancer. On the contrary, the expression of MI R-29s in other cancers is rising, such as breast cancer, nasopharyngeal carcinoma, glioma and acute myelogenous leukemia. These studies show that MI R-29a may play a role in the promotion or suppression of different cancers. However, its clinical significance, role and potential molecular mechanisms in PTC are still not very clear. In this study, we analyzed the relationship between the expression of MI R-29a and the clinicopathological features of PTC patients, and studied the role and potential of MI R-29a in PTC through a series of in vitro and in vivo tests. Objective: to clarify the role and mechanism of MI R-29a in the development of thyroid papillary carcinoma: 1. to study the expression level of MI R-29a in PTC and its role and mechanism in proliferation and migration (1) the expression of MI R-29a in 30 groups of PTC tumor tissue specimens and adjacent normal tissues by Q RT-PCR was carried out in this experiment. In order to further study the clinicopathological significance of MI R-29a expression level in PTC patients, we selected median (0.59) as the demarcation point and divided 30 PTC specimens into mi R-29a relative low level group (0.59,14 cases) and MI R-29a relative high level group (0.59,16 cases), and then used the card expression with the clinicopathological parameters. (2) in order to elucidate the biological function of MI R-29a in PTC, we transfected mi R-29a mimics into K1 cell lines and obtained a K1 cell line that stably expressed mi R-29a. To detect cell proliferation, cell cycle and apoptosis. (3) the effect of MI R-29a on the invasion and migration of PTC cells through wound healing experiments and tumor cell invasiveness experiments,.2.mi R-29a inhibits the growth of PTC by regulating AKT3 (1) we use biological information databases such as Target Scan, MI Randa, and Pic To predict the potential target gene of MI R-29a, AKT3 is locked as the research target because it plays an important role in the PI3K/AKT signaling pathway and involves a variety of cell functions. In order to verify whether AKT3 is the direct target of MI R-29a in PTC, a human AKT3 3 'UTR contains fragments of MI R-29a binding sites or cloned mutation sites. PGL3 vector, CO transfected with MI R-29a analogue or MI R-Ctrl into K1 cells, incubated 48h, and then detected the activity of luciferase. Through Q RT-PCR and Western blotting experiments, the effect of overexpression on the expression level in the cells was detected from the M proficiency level and protein level. (2) the target gene has been clearly defined. We continue to use Q RT-PCR to study the expression of AKT3 in PTC tissue and its adjacent normal tissues. (3) in order to further explore the biological effects of AKT3 in PTC, we transfect si-AKT3 and si-Ctrl into K1 cells respectively, and verify the knockout efficiency by Q RT-PCR and western. Cell proliferation was detected by colorimetric assay, cell apoptosis was detected by flow cytometry, cell migration and tumor cell invasiveness were detected by wound healing experiments. (4) in order to further study the function of AKT3 needle for MI R-29a, we designed a series of experiments on whether mi R-29a will increase in PTC cells when AKT3 is overexpressed. The effects of colonization, apoptosis, migration and invasion were evaluated. To this end, AKT3 overexpressed plasmids were transfected into K1 cells with MI R-29a analogue or MI R-Ctrl. Then MTT colorimetric assay was used to detect cell proliferation, flow cytometry was used to detect cell apoptosis, wound healing test was used to detect cell migration and tumor cell invasion test cells. The experimental study of the inhibitory effect of.3.mi R-29a on the growth of PTC in the body shows that miR-29a has the effect of inhibiting the growth of the tumor in vitro, and we then evaluate its role in the body. For this purpose, we will steadily express the K1 cells of MI R-29a or MI R-Ctrl into the subcutaneous of nude mice to form a tumor. 30 days after the injection. The animals were killed, and the tumor tissue was stripped. The size and weight of the two groups of tumors were observed and measured. In addition, we also measured the expression of MI R-29a and AKT3 in the tumor tissues by Q RT-PCR. Then, the expression level of AKT3 was measured by Q RT-PCR and Western blotting experiment. The expression level and its role and mechanism in proliferation and migration (1) the relative expression of MI R-29a in the expression of down regulated PTC in human PTC tissues by Mi R-29a is significantly lower than that of its adjacent normal tissue (P0.01). We select the median (0.59) as the demarcation point and divide the 30 PTC standard into the MI R-29a relative low level group (0.59,14 cases). 9A was compared with the high level group (0.59,16 cases), then the expression of MI R-29a and the clinicopathological parameters were analyzed with chi square test. The analysis showed that the expression of MI R-29a was not statistically significant to age and sex. At the same time, the level of MI R-29a was negatively correlated with TNM stages (P0.01), tumor size (P0.01) and lymph node metastasis. (2) mi R-29a inhibited PTC cell proliferation and induced apoptosis through Q RT-PCR to confirm that the expression level of MI R-29a increased in K1 cell lines (P0.01). MTT colorimetric assay showed that MI R-29a could significantly inhibit the proliferation of Q cells. Compared with the transfected mi R-Ctrl group, the proportion of S phase in the K1 cells of MI R-29a was reduced (P0.05), and the proportion of G0/G1 phase increased significantly (P0.01). Apoptosis experiments showed that the transfection of MI R-29a analog in K1 cell lines could significantly promote apoptosis. Compared with the MI R-Ctrl group, increasing the expression level of miR-29a significantly inhibited the ability of K1 cell invasion and metastasis (P0.01) the mechanism of.2.mi R-29a to inhibit PTC growth by regulating AKT3 (1) AKT3 is the direct target gene of MI R-29a, which obviously inhibited the luciferase activity of the wild type loci, but the mutant type The luciferase activity of the loci did not change. This indicates that AKT3 is a direct target gene for MI R-29a. Then, the Q RT-PCR and Western blotting experiments have demonstrated that MI R-29a overexpression can completely inhibit AKT3 expression in K1 cells, whether from m and protein levels. The expression of phosphorylated AKT (p-AKT) is inhibited, which suggests that MI R-29a can inhibit the activation of PI3K/AKT signal transduction pathway. The above results show that MI R-29a can be directly associated with AKT3 and inhibit its expression. (2) the expression of MI R-29a in PTC tissues is negatively related to the expression of AKT3. The expression of AKT3 was negatively correlated with the expression of MI R-29a in PTC tissue (P0.01). (3) down regulation of AKT3 expression can simulate the effect of MI R-29a overexpression using si-AKT3 to reduce the expression of AKT3 in K1 cell lines to inhibit cell proliferation and induce cell apoptosis, and also inhibit tumor finely. In other words, reducing the expression of AKT3 can simulate the effect of MI R-29a on the inhibition of tumor. (4) AKT3 overexpression can reverse the action of MI R-29a, AKT3 overexpression plasmid can increase the expression of AKT3 at m RNA level and protein level, and the expression of AKT3.AKT3 in K1 cells can promote tumor cell proliferation, migration and invasion, and inhibit the tumor cells. The effect of AKT3 overexpression reverses the inhibitory effect of MI R-29a on the tumor..3.mi R-29a inhibits the growth of PTC in the body and is compared with the injection K1/miR-Ctrl group. The tumor in the K1/miR-29a group is significantly reduced in both size and weight (P0.01). Furthermore, the expression level of MI R-29a in the tumor tissues should be significantly increased (P0.01), however. The expression level of AKT3 decreased significantly, whether at m RNA level (P0.01) or protein level. Conclusion: the expression level of 1.miR-29a is reduced in PTC tissue, and its expression level is closely related to the size of tumor, TNM staging and lymph node metastasis, and.2.mi R-29a overexpression can significantly inhibit the proliferation of PTC cells. Migration and invasion, and promoting apoptosis of PTC cells and stagnation of cell cycle in G0/G1 phase. In vivo experiments confirmed that MI R-29a overexpression can reduce the growth of tumor growth.3. in PTC cells by regulating AKT3 in xenotransplantation nude mice, miR-29a can be directly combined with the 3 'non coding region of AKT3, and the overexpressed Mi R-29a can inhibit the AKT3 table significantly. As a result, the expression of AKT3 was increased in PTC tissue, and the expression of AKT3 was negatively correlated with the expression of miR-29a in the PTC tissue, and the expression of.4. was negatively correlated with the expression of miR-29a. The expression of Si RNA to reduce the expression of AKT3 could simulate the effect of MI R-29a overexpression.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R736.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王肖琴,陳興美,徐昌良,傅燕萍;甲狀腺乳頭狀癌的超聲特征[J];中國醫(yī)學(xué)影像學(xué)雜志;2002年05期

2 吳黎敏,李航,徐衛(wèi)萍;甲狀腺乳頭狀癌92例臨床分析[J];陜西腫瘤醫(yī)學(xué);2003年01期

3 周歡,陳輝,陳賢明;囊性甲狀腺乳頭狀癌誤診1例[J];東南國防醫(yī)藥;2004年01期

4 王紅衛(wèi),洪濤,劉江華,曹仁賢,文格波;人甲狀腺乳頭狀癌高表達(dá)基因片段篩選與克隆[J];中華內(nèi)分泌代謝雜志;2004年05期

5 林艷麗,王麗曾;甲狀腺乳頭狀癌36例臨床病理分析[J];西北國防醫(yī)學(xué)雜志;2004年06期

6 王國亮;張國昌;趙瑾;李鋒;;甲狀腺乳頭狀癌發(fā)生的分子遺傳學(xué)研究[J];山東醫(yī)藥;2005年34期

7 賀清明;張修莉;師福才;;甲狀腺乳頭狀癌二次手術(shù)治療體會(huì)[J];陜西醫(yī)學(xué)雜志;2006年08期

8 何春年;張靜;邢穎;;甲狀腺乳頭狀癌的診治進(jìn)展[J];現(xiàn)代診斷與治療;2006年05期

9 梁粉花;付青;戴翠華;王剛平;李江濤;趙明春;;甲狀腺乳頭狀癌與乳頭狀增生的病理研究[J];腫瘤研究與臨床;2006年11期

10 趙爾增;;兒童和青春期甲狀腺乳頭狀癌:形態(tài)亞型、生物學(xué)行為及預(yù)后(英)[J];診斷病理學(xué)雜志;2007年01期

相關(guān)會(huì)議論文 前10條

1 王英煒;朱宏;宋月佳;戚基萍;劉娜;;甲狀腺透明變梁狀腫瘤與甲狀腺乳頭狀癌的分析[A];中華醫(yī)學(xué)會(huì)病理學(xué)分會(huì)2009年學(xué)術(shù)年會(huì)論文匯編[C];2009年

2 鄭薇;張桂芝;譚建;;甲狀腺乳頭狀癌胸骨轉(zhuǎn)移2例病例報(bào)道[A];天津市生物醫(yī)學(xué)工程學(xué)會(huì)第30次學(xué)術(shù)年會(huì)暨生物醫(yī)學(xué)工程前沿科學(xué)研討會(huì)論文集[C];2010年

3 岳林先;馬懿;鄧立強(qiáng);蔡志清;王士光;;彌漫硬化型甲狀腺乳頭狀癌的聲像圖表現(xiàn)[A];中國超聲醫(yī)學(xué)工程學(xué)會(huì)第八屆全國腹部超聲學(xué)術(shù)會(huì)議論文匯編[C];2010年

4 李沿江;劉燕娜;黃敏;章春泉;皮小蘭;蔡建華;李車英;李薇;徐翔;沈孝萍;張?jiān)姕Y;;甲狀腺乳頭狀癌聲像圖回顧分析[A];中國超聲醫(yī)學(xué)工程學(xué)會(huì)第三次全國淺表器官及外周血管超聲醫(yī)學(xué)學(xué)術(shù)會(huì)議（高峰論壇）論文匯編[C];2011年

5 王全;楊俊杰;沈強(qiáng);唐衛(wèi)華;;甲狀腺乳頭狀癌的手術(shù)范圍探討[A];2005年浙江省外科學(xué)術(shù)會(huì)議論文匯編[C];2005年

6 嚴(yán)峗;;甲狀腺乳頭狀癌的超聲診斷體會(huì)[A];2012年浙江省超聲醫(yī)學(xué)學(xué)術(shù)年會(huì)論文集[C];2012年

7 時(shí)嘉欣;田家瑋;;甲狀腺乳頭狀癌的超聲造影特點(diǎn)[A];中華醫(yī)學(xué)會(huì)第十三次全國超聲醫(yī)學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2013年

8 李逢生;韓琴芳;徐榮;;超聲造影在甲狀腺乳頭狀癌診斷中的初步研究[A];中華醫(yī)學(xué)會(huì)第十三次全國超聲醫(yī)學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2013年

9 王建紅;趙誠;劉榮桂;牛曉燕;房世保;王正濱;;橋本甲狀腺炎合并甲狀腺乳頭狀癌的超聲診斷價(jià)值[A];中國超聲醫(yī)學(xué)工程學(xué)會(huì)第八屆全國腹部超聲學(xué)術(shù)會(huì)議論文匯編[C];2010年

10 王長秋;趙文雯;魯安懷;柳劍英;梅放;張波;;甲狀腺乳頭狀癌組織壞死后礦化特征研究[A];中國礦物巖石地球化學(xué)學(xué)會(huì)第13屆學(xué)術(shù)年會(huì)論文集[C];2011年

相關(guān)博士學(xué)位論文 前10條

1 劉欣;甲狀腺乳頭狀癌風(fēng)險(xiǎn)評(píng)估研究[D];吉林大學(xué);2013年

2 劉宇飛;DLC1基因的表達(dá)與甲狀腺乳頭狀癌中淋巴管生成關(guān)系的臨床研究[D];武漢大學(xué);2014年

3 張凌;促甲狀腺激素與甲狀腺乳頭狀癌發(fā)生相關(guān)的臨床基礎(chǔ)研究[D];復(fù)旦大學(xué);2014年

4 王璐;PRDM1在橋本甲狀腺炎和甲狀腺乳頭狀癌發(fā)生中的分子機(jī)理研究[D];第四軍醫(yī)大學(xué);2015年

5 董鴻;BRAF~(V600E)突變聯(lián)合臨床及病理特征在PTC診斷、預(yù)后判斷及~(131)I療效預(yù)測中的研究[D];華中科技大學(xué);2015年

6 李銳;miR-29a通過靶向調(diào)節(jié)AKT3抑制甲狀腺乳頭狀癌生長與轉(zhuǎn)移的研究[D];吉林大學(xué);2016年

7 王偉斌;腫瘤克隆起源之爭與甲狀腺乳頭狀癌研究[D];浙江大學(xué);2010年

8 孫團(tuán)起;甲狀腺乳頭狀癌的核外分子遺傳和表觀遺傳學(xué)研究[D];復(fù)旦大學(xué);2007年

9 邊學(xué);甲狀腺乳頭狀癌組織與正常腺體組織蛋白質(zhì)的差異表達(dá)分析[D];中國協(xié)和醫(yī)科大學(xué);2007年

10 陳劍;甲狀腺乳頭狀癌臨床病理特征及分子標(biāo)記物在預(yù)測腫瘤生物學(xué)行為中的意義[D];復(fù)旦大學(xué);2012年

相關(guān)碩士學(xué)位論文 前10條

1 李瑋;甲狀腺乳頭狀癌細(xì)胞對(duì)促甲狀腺激素反應(yīng)性研究[D];河北醫(yī)科大學(xué);2015年

2 馬恒;術(shù)前PLR、NLR對(duì)甲狀腺乳頭狀癌患者術(shù)后無復(fù)發(fā)生存的預(yù)測價(jià)值[D];北京協(xié)和醫(yī)學(xué)院;2015年

3 王倩倩;CCNG2在人甲狀腺乳頭狀癌K1細(xì)胞中的表達(dá)及其對(duì)K1細(xì)胞增殖凋亡影響的研究[D];河北醫(yī)科大學(xué);2015年

4 許建輝;慢病毒介導(dǎo)CCDC67轉(zhuǎn)染甲狀腺乳頭狀癌細(xì)胞生物學(xué)活性的鑒定[D];鄭州大學(xué);2015年

5 宋廣昊;TXNIP在甲狀腺乳頭狀癌組織中的表達(dá)及臨床意義[D];河北醫(yī)科大學(xué);2015年

6 楊岳;STIP1、EMA和ER-α蛋白在甲狀腺乳頭狀癌中的表達(dá)及其意義[D];河北醫(yī)科大學(xué);2015年

7 趙愛國;TC-1在甲狀腺乳頭狀癌中的表達(dá)及臨床意義[D];鄭州大學(xué);2015年

8 鄭建;MiR-146b-5p對(duì)甲狀腺乳頭狀癌細(xì)胞TPC-1相關(guān)生物學(xué)特性的影響研究[D];鄭州大學(xué);2015年

9 楊珂;甲狀腺乳頭狀癌BRAF~(V600E)基因突變與遠(yuǎn)處轉(zhuǎn)移灶攝碘能力的相關(guān)性研究[D];北京協(xié)和醫(yī)學(xué)院;2015年

10 馬思遠(yuǎn);FoxP3對(duì)甲狀腺乳頭狀癌中NIS表達(dá)的影響及機(jī)制研究[D];鄭州大學(xué);2015年

，

本文編號(hào)：1876232