MicroRNAs（miRNA）參與癌癥的發(fā)病、細(xì)胞凋亡以及細(xì)胞生長(zhǎng),，這些miRNAs被認(rèn)為在基因調(diào)控網(wǎng)絡(luò)發(fā)揮癌基因和/或抑癌基因的功能,。
近日，雜志Tumour Biol上一則研究著重探究了在三氧化二砷（ATO）誘導(dǎo)急性早幼粒細(xì)胞白血?。ˋPL）細(xì)胞NB4細(xì)胞凋亡過程中miRNA的潛在作用,。研究人員用MTT法、尿嘧啶細(xì)胞增殖實(shí)驗(yàn),、流式細(xì)胞儀分析技術(shù)以及caspase-3活性測(cè)定實(shí)驗(yàn)確定ATO對(duì)NB4細(xì)胞株細(xì)胞凋亡影響的藥理劑量,。
提取純化未處理的和2 muM ATO處理的NB4細(xì)胞系中miRNA，并轉(zhuǎn)化為互補(bǔ)DNA,。結(jié)果發(fā)現(xiàn)三氧化二砷處理細(xì)胞后，88個(gè)miRNA中的51個(gè)miRNA出現(xiàn)差異表達(dá),，表達(dá)量提高了2倍以上,。其中，48個(gè)miRNA上調(diào)了21.65倍,，而3個(gè)miRNAs表達(dá)下調(diào)了5.19倍,。
通過文獻(xiàn)篩選發(fā)現(xiàn)，大多數(shù)這些上調(diào)的miRNA與腫瘤和/或轉(zhuǎn)移抑制基因,、細(xì)胞周期阻滯和凋亡以及抑制血管生成,、侵襲和轉(zhuǎn)移相關(guān)。
研究結(jié)果表明三氧化二砷,，能在一定濃度下調(diào)節(jié)APL細(xì)胞株相關(guān)miRNA,，其中大部分是眾所周知腫瘤和/或轉(zhuǎn)移性抑制因子，并已確認(rèn)參與細(xì)胞周期阻滯,、細(xì)胞凋亡,。這項(xiàng)研究的結(jié)果支持了miRNA可能在ATO治療急性早幼粒細(xì)胞白血病中發(fā)揮關(guān)鍵作用這一假設(shè)。（生物谷：Bioon.com）
doi:10.1007/s13277-011-0259-1
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Alteration in miRNA gene expression pattern in acute promyelocytic leukemia cell induced by arsenic trioxide: a possible mechanism to explain arsenic multi-target action.
Ghaffari SH, Bashash D, Dizaji MZ, Ghavamzadeh A, Alimoghaddam K.
MicroRNAs (miRNAs) are involved in cancer pathogenesis, apoptosis, and cell growth, and these miRNAs are thought to be functional as oncogenes and/or tumor suppressors in the gene regulatory networks. We studied the potential contribution of miRNAs in acute promyelocytic leukemia (APL) cell NB4 during the apoptosis induction by arsenic trioxide (ATO). The apoptotic effects of ATO on the NB4 cell line at a pharmacological dose (2 μM) was verified using cell growth and viability assays, MTT assay, BrdU cell proliferation assay, flow cytometric analysis, and caspase-3 activity assay. miRNAs from untreated and 2 μM ATO-treated NB4 cell line were extracted, purified, and converted to complementary DNAs. Differential expressions of 88 cancer-related miRNAs were analyzed by real-time reverse transcription PCR using miRNA PCR cancer-array system. After normalizing to the average Ct value of three housekeeping genes in the array (U6, SNORD47, and SNORD48), the fold change of miRNAs was calculated in the ATO-treated cells as compared to untreated. Among the 88 cancer-focused miRNAs, 51 miRNAs were found to be differentially expressed more than 2-fold after ATO treatment. Of these, 48 miRNAs were upregulated up to 21.65-fold changes, while three miRNAs were downregulated up to 5.19-fold changes. By screening the literature, a majority of these upregulated miRNAs were found to have tumor and/or metastatic suppressors' functions associated with cell cycle arrest and apoptosis, as well as inhibition of angiogenesis, invasion, and metastasis. Our results demonstrate that ATO, at the relevant concentration, modulate a substantial number of cancer-related miRNAs in APL cell line; most of these are known to function as a tumor and/or metastatic suppressors and have confirmed targets involved in cell cycle arrest and apoptosis. The results of this study support the hypothesis that miRNAs may play a mediatory role in eliciting the multi-target and pleiotropic action of ATO.
