MiR-26b是前列腺癌中的抑癌微RNA(英文)
發(fā)布時(shí)間:2018-05-27 23:34
本文選題:miR-b + 前列腺癌細(xì)胞 ; 參考:《生物化學(xué)與生物物理進(jìn)展》2017年06期
【摘要】:微RNAs(又稱miRNAs或miRs)是一類長(zhǎng)度為19~24個(gè)核苷酸的單鏈非編碼RNA分子.miRNA通過(guò)與其靶向的mRNA分子序列特異性互補(bǔ)配對(duì),調(diào)節(jié)mRNA表達(dá)水平,抑制轉(zhuǎn)錄后的蛋白質(zhì)翻譯.miRNA在腫瘤中既可作為致癌因子也可作為抑癌因子.本研究前期已報(bào)道m(xù)iR-26b在前列腺癌細(xì)胞系中低表達(dá),并且抑制細(xì)胞自噬.本研究進(jìn)一步全面揭示miR-26b對(duì)前列腺腫瘤細(xì)胞的作用.我們發(fā)現(xiàn)過(guò)表達(dá)miR-26b能夠在體外抑制前列腺癌細(xì)胞的增殖和侵襲,并抑制裸鼠體內(nèi)原位異種前列腺腫瘤的生長(zhǎng).為了探究miR-26b對(duì)前列腺癌細(xì)胞增殖和侵襲的潛在調(diào)控機(jī)制,我們進(jìn)行了表達(dá)譜芯片鑒定miR-26b調(diào)控基因.表達(dá)譜芯片分析表明,在前列腺癌細(xì)胞系PC-3中過(guò)表達(dá)miR-26b后,顯著上調(diào)的基因57個(gè),顯著下調(diào)的基因55個(gè)(變化倍數(shù)均大于2,且P值小于0.05).差異基因的功能多與細(xì)胞增殖、凋亡調(diào)控、蛋白質(zhì)磷酸化和泛素化修飾調(diào)控過(guò)程相關(guān),并且富集在多種信號(hào)通路中,例如TNF和TGF-β信號(hào)通路.在這些篩選出的基因中,CEACAM6表達(dá)水平下調(diào)2.17倍;序列分析及實(shí)驗(yàn)驗(yàn)證表明,CEACAM6的3′UTR區(qū)存在miR-26b的互補(bǔ)序列,是miR-26b的直接靶標(biāo).本研究證明了miR-26b能夠靶向結(jié)合抑制CEACAM6的表達(dá),從而抑制前列腺癌細(xì)胞在體外和體內(nèi)的細(xì)胞增殖和侵襲活性,miR-26b是前列腺癌中的抑癌microRNA.
[Abstract]:MicroRNas (also known as miRNAs or miRs) are a class of single-stranded non-coding RNA molecules with a length of 19~ 24 nucleotides. MiRNAs regulate the expression level of mRNA by specific complementary pairing with their targeted mRNA molecules. Inhibition of post-transcriptional protein translation. MiRNA can be used as both carcinogen and tumor suppressor in tumor. This study reported that miR-26b was expressed in prostate cancer cells and inhibited autophagy. This study further revealed the effect of miR-26b on prostate tumor cells. We found that overexpression of miR-26b could inhibit the proliferation and invasion of prostate cancer cells in vitro and inhibit the growth of xenogeneic prostate neoplasms in vivo in nude mice. In order to investigate the potential regulatory mechanism of miR-26b on the proliferation and invasion of prostate cancer cells, we identified the miR-26b regulatory gene by expression microarray. Expression microarray analysis showed that after overexpression of miR-26b in prostate cancer cell line PC-3, 57 genes were significantly up-regulated and 55 genes were significantly down-regulated (change times were more than 2, P < 0.05). The function of differentially expressed genes is closely related to cell proliferation, apoptosis, protein phosphorylation and ubiquitin modification, and is enriched in many signal pathways, such as TNF and TGF- 尾 signaling pathways. The expression level of CEACAM6 was down-regulated by 2.17 times in these selected genes, and the sequence analysis and experimental verification showed that the 3'UTR region of CEACAM6 contained complementary miR-26b sequence, which was the direct target of miR-26b. This study demonstrated that miR-26b can target to inhibit the expression of CEACAM6 and thus inhibit the cell proliferation and invasion activity of prostate cancer cells in vitro and in vivo.
【作者單位】: 西北農(nóng)林科技大學(xué)生命科學(xué)學(xué)院;Faculty
【基金】:supported by grants from National Instrumentation Program(2012YQ030261) The National Natural Science Foundation of China(31540002,31571194) Northwest A&F University Doctoral Scientific Research Fund(Z109021633)~~
【分類號(hào)】:R737.25
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本文編號(hào):1944272
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