本文選題：miR-26b　切入點(diǎn)：放射性肺損傷　出處：《重慶理工大學(xué)》2017年碩士論文

【摘要】：放射性肺損傷(Radiation-induced lung injury,RILI)是胸部腫瘤放療后常見并發(fā)癥之一,如肺癌、乳腺癌等癌癥的放療后。放射性肺損傷的早期主要表現(xiàn)為放射性肺炎,后期部分患者可發(fā)展為肺纖維化,嚴(yán)重影響患者的生活質(zhì)量,并且明顯縮短患者的生存時期。microRNA(miRNA)一直是近些年研究的熱點(diǎn)。miRNA是一類內(nèi)源性非編碼小RNA分子,長度在18-22nt之間。miRNA的表達(dá)極為廣泛,幾乎包涵了所有的生物,如植物、動物和病毒等。目前miRNA的研究也較為深入,主要是在轉(zhuǎn)錄水平上調(diào)控基因的表達(dá),它通過結(jié)合靶基因的3’非翻譯區(qū)抑制翻譯或增強(qiáng)靶mRNA的降解。人基因組中約60%的基因都受到miRNA的調(diào)控。近年來,越來越多研究表明電離輻射可以誘導(dǎo)miRNA差異表達(dá),miRNA的異常表達(dá)可能與腫瘤細(xì)胞輻射敏感性具有一定的相關(guān)性。因此,miRNA可能作為一個潛在的新的放療增敏靶點(diǎn),有望在未來在臨床上得到廣泛應(yīng)用。目前關(guān)于miRNA與放射性肺損傷之間的研究還不是很多,具體的生物學(xué)機(jī)制也不清楚。本課題是為了揭示miRNA與放射性肺損傷之間的關(guān)系,體外初步探討miRNA對放射性肺損傷發(fā)生的影響及相關(guān)機(jī)制。作者通過查閱大量文獻(xiàn),發(fā)現(xiàn)microRNA-26b(miR-26b)可能是一個潛在的較為重要的miRNA,認(rèn)為miR-26b可能在放射性肺損傷中發(fā)揮著非常重要的作用。作者采用人的支氣管上皮細(xì)胞HBE作為細(xì)胞模型,暴露于不同的輻射劑量,發(fā)現(xiàn)電離輻射會顯著上調(diào)miR-26b的表達(dá)水平;接著采用轉(zhuǎn)染技術(shù),在干擾HBE細(xì)胞中miR-26b的表達(dá)后重新暴露于電離輻射中;然后采用CCK8檢測其對細(xì)胞增殖能力的影響,通過流式細(xì)胞術(shù)分析miR-26b轉(zhuǎn)錄抑制對HBE細(xì)胞周期分布的影響。實(shí)驗(yàn)結(jié)果表明:電離輻射暴露條件下會上調(diào)HBE細(xì)胞中miR-26b的表達(dá)水平;干擾HBE細(xì)胞miR-26的表達(dá)后,電離輻射會顯著促進(jìn)HBE細(xì)胞增殖,干擾miR-26b后暴露于電離輻射下會影響HBE細(xì)胞周期,阻滯在G2/M期;通過生物信息學(xué)分析,發(fā)現(xiàn)CCND2可能是miR-26b的靶基因,miR-26可以靶向負(fù)調(diào)控CCND2的表達(dá)。通過上述研究,作者發(fā)現(xiàn)miR-26b在體外參與對人支氣管上皮細(xì)胞HBE增殖及放射敏感性的調(diào)控,其作用機(jī)制可能與其對細(xì)胞周期等相關(guān)蛋白的表達(dá)調(diào)控有關(guān),然而具體的作用途徑和分子機(jī)制還有待進(jìn)一步的深入研究。
[Abstract]:Radiation pulmonary injury (Radiation-induced lung injury, RILI) is one of the common complications after radiotherapy of thoracic tumors, such as lung cancer, breast cancer and other cancers after radiotherapy. Early radiation-induced lung injury mainly for late radiation pneumonitis, some patients may develop pulmonary fibrosis, seriously affecting the quality of life of patients and shorten the survival of patients with.MicroRNA during the period of.MiRNA (miRNA) has been a hot research in recent years is a kind of endogenous non encoding small RNA molecules, the expression of 18-22nt in length.MiRNA is very wide, it covers almost all organisms, such as plants, animal and virus. At present the research on miRNA is also deeply, is mainly regulated at the transcriptional level of gene expression it is, by combining the target gene 3 'untranslated region inhibit translation or enhanced degradation of target mRNA. About 60% genes in the genome are regulated by miRNA in recent years. And more and more research shows that ionizing radiation can induce expression of miRNA, the radiation sensitivity of tumor cells and abnormal expression of miRNA has a certain correlation. Therefore, miRNA may serve as a potential new target for radiosensitization, is expected to be widely used in clinical applications. The future researches on miRNA and radiation induced lung injury there is not a lot, specific biological mechanism is not clear. This study is to reveal the relationship between miRNA and radiation-induced lung injury in vitro, preliminary study of miRNA on the phase and shutdown influence the occurrence of radiation-induced lung injury. The author by reading a lot of literature, found that microRNA-26b (miR-26b) is potentially an important miRNA and that miR-26b may play a very important role in radiation-induced lung injury. The bronchial epithelial cells HBE as model cells, exposure In different radiation doses, the expression level of miR-26b was significantly up-regulated by ionizing radiation will be found; then the transfection, expression of miR-26b in interference in HBE cells after exposure to ionizing radiation; then using CCK8 to detect the effect on cell proliferation, through the analysis of inhibition effect on HBE cell cycle distribution of miR-26b transcription by flow cytometry FCM. The experimental results show that exposure to ionizing radiation will increase the expression level of miR-26b in HBE cells under the condition of interfering HBE expression; miR-26 cells after ionizing radiation can significantly promote the proliferation of HBE cells, miR-26b interference after exposure to ionizing radiation will affect HBE cell cycle arrest in G2/M phase; by Bioinformatics analysis. We found that CCND2 may be the target gene of miR-26b, miR-26 can express the target to the negative regulation of CCND2. Through the above research, the author found that miR-26b in vitro in on human bronchial epithelial cells The regulation of HBE cell proliferation and radiosensitivity, expression regulation and its mechanism may be related to cell cycle related proteins, but the pathway and the exact molecular mechanism still needs further research.

【學(xué)位授予單位】：重慶理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R730.55

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