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        microRNA-1290在消化系統(tǒng)腫瘤中的研究進(jìn)展

        2020-12-14 04:16:51莫輝徐岷
        中國醫(yī)藥導(dǎo)報(bào) 2020年29期
        關(guān)鍵詞:鱗癌食管癌研究進(jìn)展

        莫輝 徐岷

        [摘要] 微小RNA(microRNAs)是一類短的非編碼RNA,大量研究表明其與惡性腫瘤的發(fā)生發(fā)展密切相關(guān)。microRNA-1290作為microRNAs家族的一員,近年來越來越多的研究發(fā)現(xiàn)其在多種消化系統(tǒng)腫瘤(包括食管癌、胃癌、胰腺癌、結(jié)直腸癌、肝臟腫瘤等)中表達(dá)異常,且可能與腫瘤的增殖、侵襲、遷移、凋亡及不良預(yù)后等密切相關(guān),本文就microRNA-1290在多種消化系統(tǒng)腫瘤中研究進(jìn)展作一綜述,以期為基于microRNA-1290的抗腫瘤治療研究提供新的思路。

        [關(guān)鍵詞] 腫瘤;消化系統(tǒng);微小RNA;microRNA-1290;研究進(jìn)展

        [中圖分類號(hào)] R57? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] A? ? ? ? ? [文章編號(hào)] 1673-7210(2020)10(b)-0048-04

        [Abstract] MicroRNAs (microRNAs, miRNAs) are a type of short non-coding RNA. A large number of studies have shown that they are closely related to the occurrence and development of malignant tumors. As a member of the microRNAs family, microRNA-1290 has been increasingly researched in recent years and found in various digestive system tumors (including esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer, liver tumor, etc.) The expression is abnormal, and may be closely related to tumor proliferation, invasion, migration, apoptosis and poor prognosis. This article reviews the research progress of microRNA-1290 in various digestive system tumors, hoping to provide new ideas for anti-tumor therupy research based on microRNA-1290.

        [Key words] Tumor; Digestive system; MicroRNA; MicroRNA-1290; Research progress

        微小RNA(microRNAs)是一類小分子的、內(nèi)源性的、長度為18~25個(gè)核苷酸的單鏈非編碼RNA,過去曾被認(rèn)為是基因轉(zhuǎn)錄過程中的“噪音”。隨著研究的深入,研究者發(fā)現(xiàn)他們在腫瘤的發(fā)生、發(fā)展過程發(fā)揮不可忽視的作用,其調(diào)控機(jī)制包括轉(zhuǎn)錄修飾和轉(zhuǎn)錄后修飾,前者包括組蛋白修飾、DNA甲基化:后者與抑制mRNA翻譯和誘導(dǎo)降解密切相關(guān)[1]。本文就microRNA-1290(miR-1290)在多種消化系統(tǒng)腫瘤中研究進(jìn)展作一綜述,以期為基于miR-1290的抗腫瘤治療研究提供新的思路。

        1 miR-1290的概述

        MiR-1290定位于1號(hào)染色體(1p33.13),序列為UGGAUUUGGAUCA.,首次發(fā)現(xiàn)于人胚胎干細(xì)胞。在人類基因組中,ALDH4AL的第一個(gè)內(nèi)含子是由miR-1290編碼的[2]。多項(xiàng)實(shí)驗(yàn)發(fā)現(xiàn),miR-1290的異常上調(diào)與多種癌癥的發(fā)生發(fā)展息息相關(guān),如非小細(xì)胞肺癌[3]、口腔鱗狀細(xì)胞癌[4]、高級別漿液性卵巢癌[5]等。一項(xiàng)最新的薈萃分析表明miR-1290在實(shí)體瘤患者外泌體中的高表達(dá)往往意味著較差的總體生存率[6]。

        2 miR-1290與消化系統(tǒng)腫瘤

        2.1 miR-1290與食管癌

        食管癌是最常見的消化道腫瘤之一[7],每年有超過48 000中國人患上了食管癌,是中國惡性腫瘤死亡的第四大主要原因[8],食管癌發(fā)生發(fā)展的早期診斷較為困難,且晚期食管癌常伴有廣泛的局部浸潤或區(qū)域性淋巴結(jié)轉(zhuǎn)移,即使手術(shù)后5年生存率仍然在20%[9]。故而,熟悉食管癌發(fā)生和發(fā)展的分子機(jī)制對于確定食管癌新的治療靶點(diǎn)起到至關(guān)重要的作用,早期關(guān)于分子機(jī)制的研究證實(shí)了RoAl-DIA1信號(hào)轉(zhuǎn)導(dǎo)通路中的SCAI是miR-1290的靶基因之一,過表達(dá)的miR-1290顯著加速了食管癌細(xì)胞ECA109和TE13細(xì)胞的遷移[10]。與癌旁組織和健康對照組比較,Mao等[11]采用熒光定量PCR發(fā)現(xiàn)食管癌組織及血清中miR-1290表達(dá)上調(diào),且與NFIX蛋白呈負(fù)相關(guān),進(jìn)一步體外研究采用雙熒光素酶聯(lián)合小干擾RNA技術(shù)揭示了miR-1290可能通過作用于NFIX mRNA的3′-UTR來抑制nFIX表達(dá),從而促進(jìn)食管癌細(xì)胞的增殖、遷移和侵襲。同樣的,Sun等[12]通過收集臨床樣本也發(fā)現(xiàn)與對照組比較,食管鱗癌組織和血清miR-1290水平均顯著升高。Pearson相關(guān)性分析提示兩者高度相關(guān),多因素分析顯示,血清miR-1290是食管癌的獨(dú)立危險(xiǎn)因素。ROC曲線分析表明血清miR-1290可有效地區(qū)分食管鱗癌患者和正常對照組。且miR-1290的升高與患者有無淋巴結(jié)轉(zhuǎn)移、分化程度、TNM分期存在顯著相關(guān)性。生存分析顯示高血清miR-1290常伴有不良的預(yù)后,提示miR-1290可作為診斷和判斷預(yù)后的生物標(biāo)志物。Xie等[13]通過分析檢測100例樣本中miR-1290表達(dá)水平也得出了相同的結(jié)論,當(dāng)與靶基因NFIX聯(lián)合評估時(shí),可以作為合適的診斷和預(yù)測預(yù)后的食管癌生物標(biāo)志物。當(dāng)然這需要進(jìn)行大規(guī)模多中心研究,以驗(yàn)證方案的敏感性和準(zhǔn)確性。以上研究表明不僅為食管癌的早期診斷提供了新的思路,同時(shí)也為闡明食管癌的發(fā)病機(jī)制提供了一定的幫助。

        3 小結(jié)和展望

        綜上所述,目前miR-1290在各種消化系統(tǒng)腫瘤中的研究取得了突破性的進(jìn)展,其在腫瘤的生長、轉(zhuǎn)移以及化療耐藥性方面發(fā)揮著不可忽視的作用。盡管我們對于miR-1290在腫瘤中的作用得到了一定的認(rèn)知,但是,腫瘤的發(fā)生發(fā)展不是單因素的,miR-1290的研究還有待繼續(xù)深入,相信隨著研究的不斷深入,miR-1290有望在消化道腫瘤的預(yù)測、診斷和靶向治療中體現(xiàn)出重要的價(jià)值。

        [參考文獻(xiàn)]

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        (收稿日期:2020-06-08)

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