本文關(guān)鍵詞：長鏈非編碼RNA SNHG16調(diào)控乳腺癌細胞遷移的分子機制研究　出處：《山東大學》2017年博士論文　論文類型：學位論文

  更多相關(guān)文章： 乳腺癌 SNHG16 miR-98 E2F5 競爭性內(nèi)源RNA 細胞遷移

【摘要】：在中國,乳腺癌已經(jīng)成為發(fā)病率最高的女性惡性腫瘤。根據(jù)國家癌癥中心2015年的統(tǒng)計數(shù)據(jù)顯示,乳腺癌不僅占據(jù)了女性新發(fā)腫瘤總數(shù)的15%,也是45歲以下女性因惡性腫瘤死亡的首要病因。更為嚴峻的是,當前我國乳腺癌的發(fā)病率和死亡率都呈上升趨勢,嚴重危害著廣大女性的健康和生命。實體腫瘤患者的發(fā)病和死亡一般由擴散的腫瘤細胞對機體正常功能的破壞導致,因此腫瘤細胞遷移已成為癌癥轉(zhuǎn)移潛在機制研究的一大熱點。然而,介導乳腺癌細胞遷移的分子機制并不十分明確,可預(yù)測其進展轉(zhuǎn)移的分子標志物仍然有限。發(fā)現(xiàn)乳腺癌進展轉(zhuǎn)移過程中的關(guān)鍵分子及調(diào)節(jié)通路是乳腺癌研究中的重點,有助于指導乳腺癌早期診療從而降低病死率改善預(yù)后。長鏈非編碼RNA(long noncoding RNA,lncRNA)是近年來發(fā)現(xiàn)的一類不編碼蛋白質(zhì)的,長度超過200bp的RNA分子,許多文獻報道lncRNA在腫瘤進展轉(zhuǎn)移的過程中發(fā)揮重要作用�，F(xiàn)有研究表明,lncRNA通過多種機制發(fā)揮抑癌或促癌功能,其中l(wèi)ncRNA與miRNA之間的相互作用機制主要有:miRNA結(jié)合并降解 lncRNA,lncRNA 作為 miRNA 海綿(miRNA sponge)結(jié)合吸附 miRNA,以及l(fā)ncRNA截短生成miRNA等。長鏈非編碼 RNA SNHG16 全稱為 small nucleolar RNA host gene 16,即核內(nèi)小 RNA 宿主基因 16,又叫 non-coding RNA expressed in aggressive neuroblastoma(ncRAN),是一種最早在神經(jīng)母細胞瘤中發(fā)現(xiàn)的lncRNA,并且被證明在結(jié)直腸癌和膀胱癌中有促癌作用。然而,SNHG16是否影響乳腺癌的進展轉(zhuǎn)移及其作用機制尚無報道。因此,本課題旨在研究SNHG16在乳腺癌進展轉(zhuǎn)移中的作用及其涉及的分子生物學機制。研究內(nèi)容主要分為以下四個部分:一.SNHG16在乳腺癌中的異常表達及其對乳腺癌細胞增殖和遷移能力的影響;二.SNHG16在乳腺癌中發(fā)揮作用的關(guān)鍵下游miRNA和競爭性內(nèi)源RNA的預(yù)測及驗證;三.SNHG16的下游分子miR-98和E2F5在乳腺癌細胞遷移中的功能及二者之間的靶向作用驗證;四.SNHG16對E2F5的調(diào)節(jié)作用及對乳腺癌細胞遷移功能的影響依賴于miR-98。第一部分SNHG16在乳腺癌中的異常表達及其對乳腺癌細胞增殖和遷移能力的影響目的:以往研究表明SNHG16在神經(jīng)母細胞瘤、膀胱癌以及結(jié)直腸癌中異常高表達,并發(fā)揮促癌的作用。但是SNHG16在乳腺癌中的功能尚不清楚。本研究首先確定乳腺癌組織標本中SNHG16的表達水平,再通過調(diào)控乳腺癌細胞系中SNHG16的表達來進行體外實驗以確定其對乳腺癌細胞增殖遷移能力的影響。方法:收集乳腺癌腫瘤組織及癌旁非腫瘤組織共30對,提取總RNA并反轉(zhuǎn)錄,通過相對實時定量PCR(qRT-PCR)檢測乳腺癌腫瘤組織及癌旁非腫瘤組織中SNHG16的表達差異。同時檢測常用乳腺癌細胞系中SNHG16的表達水平,選取表達量較高的細胞系進行干擾實驗,表達量較低的細胞系進行過表達實驗。采用MTT實驗測定SNHG16對乳腺癌細胞增殖能力的影響。通過Transwell細胞遷移實驗中穿過小室濾膜的細胞數(shù)目來檢測調(diào)控SNHG16表達后細胞遷移能力的改變。結(jié)果:QRT-PCR結(jié)果表明,30對乳腺組織中有21對中的SNHG16在乳腺癌組織比正常組織表達升高。SNHG16在MDA-MB-231和MCF-7細胞系中表達量較高,在MDA-MB-468和SK-BR-3細胞系中表達較低。MTT實驗證明SNHG16對乳腺癌細胞增殖無明顯作用。Transwell實驗結(jié)果表明在MDA-MB-231和MCF-7細胞系中干擾SNHG16后,細胞遷移能力下降;在MDA-MB-468和SK-BR-3細胞系中過表達SNHG16后,細胞遷移能力增強。結(jié)論:SNHG16在乳腺癌中具有促癌作用,能夠增強乳腺癌細胞的遷移能力,對乳腺癌細胞增殖無明顯作用。第二部分SNHG16在乳腺癌中發(fā)揮作用的關(guān)鍵下游miRNA和競爭性內(nèi)源RNA的預(yù)測及驗證目的:近年來的研究表明,長鏈非編碼RNA可能參與競爭性內(nèi)源RNA(competitive endogenous RNA,ceRNA)調(diào)控網(wǎng)絡(luò)從而發(fā)揮功能。為了進一步探究SNHG16在乳腺癌中發(fā)揮作用的分子生物學機制,本研究首先應(yīng)用生物信息學方法預(yù)測SNHG16可能相互調(diào)控的ceRNA及共同作用的miRNA,并通過一系列分子生物學實驗驗證SNHG16與下游miRNA的直接結(jié)合,最后在乳腺癌組織中進一步驗證SNHG16與下游miRNA的相關(guān)性。方法:通過數(shù)據(jù)庫預(yù)測SNHG16可能相互調(diào)控的ceRNA及其共同作用的miRNA,干擾或過表達SNHG16后,采用qRT-PCR實驗檢測候選ceRNA及miRNA的表達量改變,從而進一步鑒定SNHG16的關(guān)鍵下游分子。通過DIANA TOOLS預(yù)測二者與其共同作用的miRNA相互結(jié)合的位點,構(gòu)建相應(yīng)的工具載體及其結(jié)合位點突變載體,進行RNA免疫共沉淀(RIP)實驗和熒光素酶報告基因?qū)嶒?luciferase reporter assay)驗證SNHG16與下游miRNA的直接結(jié)合和具體結(jié)合位點。同時qRT-PCR檢測過表達候選miRNA后SNHG16的表達水平,進一步驗證二者之間的相互作用。最后在乳腺癌組織中檢測SNHG16與候選下游miRNA的表達水平并進行相關(guān)性分析。結(jié)果:從starBase數(shù)據(jù)庫預(yù)測SNHG16可能相互調(diào)控的ceRNA包括Rap2B,HMGA2,AMOT,SMAD2,E2F5,ZEB1等。按照競爭性內(nèi)源RNA調(diào)控理論,干擾SNHG16后,候選ceRNA的表達會由于二者之間共同的miRNA增多而減少;而過表達SNHG16后,候選ceRNA的表達會由于二者之間共同的miRNA減少而增多。因此,分別過表達和干擾SNHG16后進行qRT-PCR實驗驗證SNHG16與候選ceRNA的調(diào)控關(guān)系,結(jié)果表明干擾或過表達SNHG16后,E2F5表達量出現(xiàn)了相應(yīng)下降或增多,而其他候選ceRNA的表達量未出現(xiàn)明顯一致的變化,進一步提示E2F5很有可能為SNHG16的ceRNA。隨后通過DIANA TOOLS預(yù)測二者與其共同作用的miRNA及相互結(jié)合的位點,并通過qRT-PCR實驗驗證SNHG16可能對miR-98具有海綿吸附作用(miRNA sponge)。構(gòu)建野生型和突變型載體,進行RNA免疫共沉淀實驗和熒光素酶報告基因?qū)嶒炦M一步驗證SNHG16與下游miR-98的直接結(jié)合和具體結(jié)合位點。過表達miR-98后SNHG16表達降低,進一步證明SNHG16與miR-98之間的相互作用。QRT-PCR結(jié)果統(tǒng)計分析表明,在乳腺癌組織中SNHG16與miR-98的表達水平呈顯著負相關(guān)。結(jié)論:SNHG16與miR-98存在直接相互結(jié)合作用,可能作為ceRNA與E2F5競爭性結(jié)合miR-98從而發(fā)揮促癌功能。第三部分SNHG16的下游分子miR-98和E2F5在乳腺癌細胞遷移中的功能及二者之間的靶向作用驗證目的:為了探究SNHG16是否通過miR-98和E2F5這一調(diào)控軸線在乳腺癌中發(fā)揮作用,對于下游分子miR-98和E2F5在乳腺癌中的功能及二者之間的靶向作用需要進一步驗證。方法:首先在乳腺癌細胞中過表達miR-98后進行Transwell細胞遷移實驗,并進行統(tǒng)計分析驗證miR-98對乳腺癌細胞遷移的影響。通過熒光素酶報告基因?qū)嶒灐RT-PCR及Western Blot(蛋白免疫印記)實驗驗證miR-98與E2F5的直接靶向作用。通過干擾E2F5后的Transwell實驗驗證E2F5在乳腺癌細胞遷移中的作用。最后檢測乳腺癌腫瘤組織及癌旁非腫瘤組織中E2F5的表達差異并進行統(tǒng)計分析證明E2F5在乳腺癌中的功能。結(jié)果:Transwell細胞遷移實驗證明過表達miR-98或干擾E2F5后能夠顯著抑制乳腺癌細胞遷移。熒光素酶報告基因?qū)嶒�、qRT-PCR及Western Blot實驗證明miR-98能夠直接靶向E2F5并調(diào)控其表達。30對乳腺組織中有23對中的E2F5在乳腺癌組織比正常乳腺組織表達升高。結(jié)論:miR-98能夠顯著抑制乳腺癌細胞遷移,E2F5作為miR-98的直接靶基因,干擾其表達后也能發(fā)揮類似功能。第四部分SNHG16對E2F5的調(diào)節(jié)作用及對乳腺癌細胞遷移功能的影響依賴于miR-98目的:為了證明SNHG16是通過與E2F5競爭性結(jié)合miR-98發(fā)揮促進乳腺癌細胞遷移的功能,我們進一步探究SNHG16對E2F5的調(diào)節(jié)作用并驗證這種調(diào)節(jié)作用和SNHG16對乳腺癌細胞遷移功能的影響是否依賴于miR-98。方法:在MDA-MB-231和MCF-7細胞系中干擾SNHG16或在MDA-MB-468和SK-BR-3細胞系中過表達SNHG16后,通過qRT-PCR及Western Blot實驗檢測E2F5的表達變化。在乳腺癌細胞系和乳腺癌組織中檢測SNHG16和E2F5的表達水平并進行相關(guān)性分析。進行"挽救"(rescue)實驗即共轉(zhuǎn)染SNHG16和miR-98觀察miR-98是否可以逆轉(zhuǎn)SNHG16對乳腺癌細胞遷移能力的增強作用以及對E2F5的調(diào)控作用。結(jié)果:QRT-PCR及Western Blot實驗結(jié)果表明干擾SNHG16后,E2F5表達量降低;過表達SNHG16后,E2F5表達量升高。在乳腺癌細胞系和乳腺癌組織中SNHG16和E2F5的表達水平呈顯著正相關(guān),也從側(cè)面驗證了 SNHG16對E2F5的正調(diào)控作用。Rescue實驗結(jié)果表明,與SNHG16共轉(zhuǎn)染入miR-98后,miR-98能夠部分消除SNHG16介導的細胞遷移增強以及SNHG16對E2F5的正調(diào)控作用。結(jié)論:SNHG16對E2F5的表達具有正調(diào)控作用,并且SNHG16對E2F5的調(diào)節(jié)作用及對乳腺癌細胞遷移功能的影響依賴于miR-98。本論文重點闡述了 SNHG16在乳腺癌進展轉(zhuǎn)移中的功能及其具體作用的分子機制。創(chuàng)新之處主要表現(xiàn)為以下幾點:1.首次對SNHG16在乳腺癌細胞遷移中的作用進行探究并證明SNHG16發(fā)揮作用依賴于miR-98;2.首次提出SNHG16作為競爭性內(nèi)源RNA與E2F5競爭性結(jié)合miR-98從而發(fā)揮作用;3.通過RNA免疫共沉淀和熒光素酶報告基因?qū)嶒烌炞C了 SNHG16與miR-98的直接結(jié)合,并設(shè)計突變載體證實了數(shù)據(jù)庫預(yù)測的結(jié)合位點;4.揭示了 SNHG16在乳腺癌中對E2F5的正向調(diào)控作用。本論文尚存在一些不足,也是我們未來的研究方向,主要存在以下幾點:1.論文主要對SNHG16在乳腺癌細胞增殖和遷移方面的功能進行了探究,尚未在乳腺癌細胞侵襲、凋亡、化療耐藥等方面發(fā)現(xiàn)明顯調(diào)控功能,需要進一步研究。2.課題主要利用乳腺癌細胞系進行了體外實驗研究SNHG16對乳腺癌轉(zhuǎn)移的影響,尚需包括裸鼠成瘤及肺轉(zhuǎn)移模型等體內(nèi)實驗進一步完善SNHG16在乳腺癌中作用功能的探究。3.本研究在臨床標本中僅對SNHG16和下游分子在乳腺癌組織及癌旁非腫瘤組織中進行了表達差異及相關(guān)性分析,尚未與目前現(xiàn)有的乳腺癌分型指標進行對比研究,需要進一步擴大標本量進行明確的病理分型分析。
[Abstract]:In China, breast cancer has become the highest incidence of malignant tumor in women. According to the statistics in 2015 the National Cancer Center showed that breast cancer not only occupy 15% of the total number of female primary tumor, but also women under the age of 45 because the primary cause of death of malignant tumors. The more serious is that the incidence of breast cancer in China and death rates are on the rise, serious harm to women's health and life. Lead to destruction of morbidity and mortality in patients with solid tumors by diffusion of tumor cells to normal physiological function, so the migration of tumor cells has become a hot research topic in the mechanisms underlying metastasis of cancer. However, mediated molecular mechanism of breast cancer cells the migration is not very clear, molecular markers can predict the progression of metastasis is still limited. To find the key molecule in the process of metastasis of breast cancer progression and regulation pathway is breast cancer The focus of research, is helpful for the early diagnosis and treatment of breast cancer so as to reduce the mortality and improve the prognosis. Long chain encoding RNA (long noncoding non RNA, lncRNA) is a newly discovered class of encoding protein, RNA molecular length of more than 200bp, many reported that lncRNA play an important role in tumor progression and metastasis in the current study shows that lncRNA, through a variety of mechanisms play a tumor suppressor or cancer promoting function, the interaction mechanism between lncRNA and miRNA are: miRNA binding and degradation of lncRNA, lncRNA as miRNA (miRNA sponge) combined with sponge adsorption miRNA, and generate miRNA. LncRNA truncated long chain non encoding RNA SNHG16 small nucleolar RNA host gene 16, the small nuclear RNA gene 16, also called non-coding RNA expressed in aggressive neuroblastoma (ncRAN), is one of the earliest in neuroblastoma cells in tumor Now lncRNA, and proved in the colorectal cancer and bladder cancer in the cancer promoting effects. However, the influence of SNHG16 on metastasis and mechanism of breast cancer has not been reported. Therefore, the purpose of this paper is to study the role of SNHG16 in progression of metastasis in breast cancer and its mechanism of molecular biology. The research contents are mainly divided into the following four parts: the abnormal expression of.SNHG16 in breast cancer and its effect on the proliferation and migration of breast cancer cells; the prediction and verification of two.SNHG16 play a role in breast cancer miRNA key downstream and competitive endogenous RNA; between three.SNHG16 downstream molecules miR-98 and E2F5 in breast cancer cell migration in the function and the two target verification; four the regulative effect of.SNHG16 on E2F5 and the influence on the function of breast cancer cell migration depends on the first part of the miR-98. abnormal expression of SNHG16 in breast carcinoma The influence on the proliferation and migration of breast cancer cells Objective: Previous studies showed that SNHG16 in neuroblastoma, bladder cancer and colorectal cancer in abnormal high expression, and play the role of promoting cancer. But the SNHG16 function in breast cancer is unclear. In this study, to determine the expression level of SNHG16 mammary gland carcinoma specimens the in vitro experiment to the regulation of SNHG16 expression in breast cancer cell lines to determine their impact on proliferation and migration of breast cancer cells. Methods: We collected and cancer of breast tumor adjacent non tumor tissue of a total of 30, total RNA extraction and reverse transcription by relative quantitative real-time PCR (qRT-PCR) detection breast cancer tumor tissues and non differential expression of SNHG16 in tumor tissue. At the same time to detect the expression of SNHG16 in breast cancer cell lines, select the interference experiment high expression cell lines, expression Low cell lines were overexpression experiments. Determination of effects of SNHG16 on cell proliferation of human breast cancer by MTT assay. Transwell cell migration by cell number through the experiment to detect the cell membrane regulates the expression of SNHG16 after the changes of cell migration. Results: QRT-PCR results showed that 30 of the breast tissues of 21 SNHG16 in breast cancer tissue than normal tissue expression increased.SNHG16 expression was higher in MDA-MB-231 and MCF-7 cell lines, expression in MDA-MB-468 and SK-BR-3 cell lines with low.MTT experiments show that SNHG16 on the proliferation of breast cancer cells had no obvious effect of.Transwell experimental results show that the interference of SNHG16 in MDA-MB-231 and MCF-7 cell lines, cell migration decreased; overexpression of SNHG16 in MDA-MB-468 and SK-BR-3 cell lines, cell migration ability. Conclusion: SNHG16 has a tumor promoting role in breast cancer, can increase The migration ability of breast cancer cells, has no obvious effect on the proliferation of breast cancer cells. The prediction and verification of purpose of the second part of the role of SNHG16 in breast cancer in key downstream miRNA and competitive endogenous RNA: recent studies show that long chain non encoding RNA may participate in the competition of endogenous RNA (competitive endogenous RNA, ceRNA) to play regulatory network function. In order to further explore the molecular mechanism of SNHG16 play a role in breast cancer, in this study we used bioinformatics methods to predict SNHG16 may regulate each other jointly by ceRNA and miRNA, and by directly binding to a series of molecular biology experiments of SNHG16 and miRNA downstream, finally verify the correlation SNHG16 and downstream of miRNA in breast cancer. Methods: the database may predict SNHG16 mutual regulation ceRNA and their interaction with miRNA, Interference or overexpression of SNHG16, the expression of qRT-PCR and miRNA ceRNA experiment to detect candidate key changes, thus further downstream molecular identification of SNHG16 DIANA TOOLS. Through the combination of the two forecast together with the miRNA site, and the corresponding construction tool carrier binding site mutant vector RNA immunoprecipitation (RIP) experiment and luciferase reporter assay (luciferase reporter assay) with direct verification of SNHG16 and downstream miRNA and specific binding sites. At the same time, qRT-PCR detected the expression level of SNHG16 expression of candidate miRNA, further verify the interaction between the two. The detection of SNHG16 and miRNA and the expression level of candidate downstream in breast cancer correlation analysis. Results: the prediction of SNHG16 may regulate each other ceRNA including Rap2B, HMGA2, AMOT, SMAD2, E2F5, ZEB1 from starBase database. According to the According to the competitive regulation of endogenous RNA interference theory, SNHG16, expression of candidate ceRNA decreases due to the increase in miRNA in common between the two; and the expression of SNHG16, expression of candidate ceRNA that increases due to the decrease of miRNA in common between the two. Therefore, the regulation relationship between expression and interference after the SNHG16 qRT-PCR experiment verify the SNHG16 and candidate ceRNA, results show that the interference or overexpression of SNHG16, E2F5 expression appeared decreased or increased, whereas the expression of other candidate ceRNA showed no obvious consistent changes, further suggesting that E2F5 is likely to SNHG16 ceRNA. followed by DIANA TOOLS two and predict the joint effect of miRNA and the interaction site of qRT-PCR, and through experimental verification of SNHG16 may have a sponge adsorption effect on miR-98 (miRNA sponge). Wild type and mutant vector construction, RNA co immunoprecipitation experiments And the luciferase reporter assay further verified with SNHG16 and downstream miR-98 and specific binding sites. Overexpression of SNHG16 decreased the expression of miR-98, further proof that.QRT-PCR result analysis of interaction between SNHG16 and miR-98, in breast cancer tissues, the expression level of SNHG16 and miR-98 showed a significant negative correlation. Conclusion: SNHG16 and miR-98 the direct interaction between ceRNA and E2F5, may serve as a competitive binding of miR-98 to promote tumor function. Between the third part of the SNHG16 downstream molecules miR-98 and E2F5 in breast cancer cell migration function and two targeting Test Objective: To explore whether SNHG16 through miR-98 and E2F5 control of this axis in breast cancer play a role for downstream molecules miR-98 and E2F5 function in breast cancer and two targeting methods need to be further verified: The expression of miR-98 in breast cancer cells after Transwell cell migration experiments and statistical analysis to verify the effect of miR-98 on the migration of breast cancer cells. The luciferase reporter assay, qRT-PCR and Western Blot (Western blot) directly target experimental verification of miR-98 and E2F5 to Transwell. Through experimental verification of E2F5 interference E2F5 the role in breast cancer cell migration. Finally, the detection of breast cancer tumor tissues and non differential expression of E2F5 in tumor tissue and statistical analysis showed that the E2F5 function in breast cancer. Results: Transwell cell migration experiments showed that overexpression of miR-98 or E2F5 interference can inhibit breast cancer cell migration luciferase reporter. The qRT-PCR and Western gene, Blot miR-98 can be proved directly targeting E2F5 and its regulation on the expression of.30 in breast tissue of 23 in E 2F5 in breast cancer tissue than in normal breast tissue expression. Conclusion: miR-98 can significantly inhibit the migration of breast cancer cells, E2F5 as a direct target gene of miR-98 interference expression can also play a similar role function. The fourth part of the SNHG16 of E2F5 and the influence on the function of breast cancer cell migration depends on the objective: to miR-98 SNHG16 was proved by miR-98 combined with E2F5 competition to promote breast cancer cell migration function, we further explore the regulatory role of SNHG16 on E2F5 and verify the regulation effect and SNHG16 on the function of breast cancer cell migration is dependent on the miR-98. method in MDA-MB-231 and MCF-7 cell lines in SNHG16 or MDA-MB-468 interference and SK-BR-3 cells in the over expression of SNHG16, expression of qRT-PCR and Western by Blot assay. E2F5 in breast cancer cells and breast cancer tissues. Correlation analysis was performed to detect the SNHG16 and E2F5 expression level. The "save" (rescue) is the experimental co transfection of SNHG16 and miR-98 on miR-98 can enhance the reversal effect of SNHG16 on the migration of breast cancer cells and the effect on the regulation of E2F5. Results: QRT-PCR and Western Blot showed that the interference SNHG16, the expression of E2F5 decreased; after overexpression of SNHG16, E2F5 expression increased. There was a positive correlation between the level of SNHG16 in breast cancer cells and breast cancer tissues and E2F5, also from the side to verify the SNHG16 of E2F5 positive role in the regulation of experimental results show that the.Rescue and SNHG16 were co transfected into miR-98, miR-98 can eliminate the SNHG16 cell migration regulation effect of SNHG16 on enhancement and E2F5. Conclusion: the expression of SNHG16 has a positive regulatory effect on E2F5, and the effect of SNHG16 on E2F5 and on the migration of breast cancer cells The effect depends on the miR-98. this paper focuses on the molecular mechanism of SNHG16 in the progression and metastasis of breast cancer. The function and specific role innovation mainly as follows: 1. for the first time on the role of SNHG16 in breast cancer cell migration to explore and prove the role of SNHG16 depends on the miR-98 of SNHG16 is proposed as 2.; the competition of endogenous RNA and E2F5 competitive binding miR-98 can play a role; 3. RNA by immunoprecipitation and luciferase assay verified the direct combination of SNHG16 and miR-98, and the design of the mutant vector confirmed the binding site prediction database; 4. reveals the positive regulation effect of SNHG16 on E2F5 in breast cancer. This thesis is there are some shortcomings, but also our future research direction, mainly has the following several points: 1. the main thesis of SNHG16 in breast cancer cell proliferation and migration of the The function of the inquiry, yet in the invasion, apoptosis of breast cancer cells, chemotherapy resistance etc. obvious regulation function, the need for further research project mainly uses the.2. breast cancer cell lines by in vitro experiment to study the effect of SNHG16 on breast cancer metastasis, still need to include the tumorigenicity and lung metastasis model in vivo to further improve in SNHG16 breast cancer in this study and Research on.3. function in clinical specimens only on SNHG16 and downstream molecules in breast cancer tissues and adjacent non tumor tissues were analyzed and the correlation between the expression of differences, not with the existing classification of breast cancer index

【學位授予單位】：山東大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R737.9

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