MiR-193a-3p與腫瘤相關性的研究

張 鏨，林茂松

（泰州市人民醫院，江蘇 泰州 225500）

microRNAs（miRNA）是一組約22個核苷酸的長度的RNA。其可以通過序列特異性的方式，直接結合到靶基因的3’UTR（3’非翻譯區）來影響翻譯及翻譯穩定性。

1 miR-193a-3p與消化系統腫瘤

Joel Pekow等人明確發現，miR-193a-3p的表達量在潰瘍性結腸炎發展為腫瘤的過程中是下降的，它通過自身表達量的減少，直接上調IL17RD，從而起到致癌作用[1]。Lin M研究表明結直腸癌患者中miR-193a-3p含量較低的患者的預后更差[2]。在食管癌細胞中mir-193a-3p表達量與化療敏感性和放射敏感性相關。mir-193a-3p可能部分通過影響PSEN1基因功能，增強放化療抵抗作用[3]。但在肝細胞癌中，mir-193a-3p的表達量是降低的[4]。

2 miR-193a-3p與呼吸系統腫瘤

miR-193a-3p直接結合到ERBB4和S6K2基因的3’非翻譯區，抑制ERBB信號通路，達到抑癌的效果[5]。還研究發現，miR-193a-3p通過接合至KRas基因，抑制肺癌細胞的生長、增殖、轉移能力[6]。miR-193a-3p 和AEG-1應對肺癌的致癌以及轉移作用中起作用，AEG-1可能成為miR-193a-3p潛在的靶基因[7]。惡性胸膜間皮瘤是石棉誘發的癌癥，其預后較差，研究發現miR-193a-3p在該疾病中是表達量下降，是潛在的抑癌基因[8]。

3 miR-193a-3p與泌尿系統腫瘤

miR-193a-3p通過對DNA的甲基化，抑制SRSF2，PLAU和HIC2基因，影響膀胱癌的多重耐藥性，為膀胱癌的診斷和治療提供新的思路[9]。LOXL4[10]和HOXC9[11]分別受到miR-193a-3p的直接調控抑制，提升了膀胱癌的多重耐藥性。基因ING5受到miR-193a-3p的調控，激活DNA損傷反應通路，抑制膀胱癌的多重耐藥性[12]。前列腺癌也是泌尿系統中較為常見的腫瘤之一，其預后與轉移密切相關，雄激素受體調節mirna-193a-3p直接結合到基因AJUBA上促進前列腺癌細胞的遷移，進而促進前列腺癌的轉移[13]。腎細胞癌是泌尿系最常見的腫瘤，mirna-193a-3p被發現直接結合到基因PTEN上，發揮抑制腎癌細胞的活性的作用[14]。

4 miR-193a-3p與乳腺癌

NLN、CCND1、PLAU、SEPN1在乳腺癌細胞中均為miR-193a-3p直接調控的靶基因。miR-193a-3p能夠通過直接結合到相關靶基因3’非翻譯區，參與抑制乳腺癌細胞的生長、遷移和侵襲能力[15]。

5 miR-193a-3p與骨肉瘤

XIST / mir-193a-3p/RSF1軸共同參與對骨肉瘤細胞功能的調控，其可能發展和作為一個治療靶點[16]。mir-193a-3p也可以通過抑制Rab27B的表達，抑制骨肉瘤的轉移，在此過程中TGFβ、Myc/Max、ATF2/ATF3/ATF4信號通路均受到抑制[17]。

6 展 望

越來越多的證據表明，miRNA的異常表達在腫瘤的發生與發展中起著重要作用，miR-193a-3p在諸多惡性腫瘤中起到抑制腫瘤細胞生長的作用，涉及諸多靶點基因，其有可能成為惡性腫瘤診斷和治療的新靶點。

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