MALAT1在结直肠癌组织细胞中的表达及对化疗敏感性的影响

[摘要] 目的 探讨MALAT1在结直肠癌组织细胞中的表达及对化疗敏感性的影响，并对其机制进行初步研究。 方法 收集首都医科大学附属北京友谊医院普外科2015年6～12月手术切除结直肠癌组织33例及相应癌旁正常组织33例，采用RT-PCR方法检测MALAT1的表达水平；采用慢病毒敲减MALAT1后，检测MALAT1在结直肠癌细胞sw620及sw480中的表达水平；MTS方法检测MALAT1在结直肠癌增殖及化疗疗效中的作用，Western blot检测相关通路蛋白表达变化。 结果 结直肠癌组织中MALAT1的表达水平较癌旁正常组织显著增高（t = 4.138，P = 0.009），慢病毒si-MALAT1显著敲减MALAT1的表达水平。MALAT1敲减后，sw620及sw480细胞的增殖均减低（t = 2.957，P = 0.009；t = 1.936，P = 0.017），且对氟尿嘧啶、奥沙利铂的敏感性增加。下调MALAT1后，PI3K及p-AKT的水平下调，而总AKT水平无明显变化。 结论 MALAT1在结直肠癌增殖及耐药过程中发挥重要作用，其可能成为结直肠癌潜在的治疗靶点。

[关键词] 结直肠癌；MALAT1；化疗；耐药

[中图分类号] R735.35 [文献标识码] A [文章编号] 1673-7210（2016）11（b）-0012-05

[Abstract] Objective To explore the expression of MALAT1 in colorectal cancer tissue cells and its influence for the chemotherapy sensitivity， in order to preliminary study the mechanism. Methods Thirty-three cases with colorectal cancer tissue and 33 cases with normal tissue adjacent to carcinoma in Department of General Surgery， Beijing Friendship Hospital， Capital Medical University from June to December 2015 were collected and performed RT-PCR method to detect the levels of MALAT1. After introducing the lentivirus to knock down MALAT1， the expression levels of MALAT1 in sw620 and sw480 of colorectal carcinoma cells were detected. MTS method was used to detect the effectiveness of proliferation and chemotherapy resistance in colorectal cancer. Western blot detection was adopted to detect the protein expression changes of related pathways. Results The expression levels of MALAT1 in colorectal cancer tissue were significantly higher than the normal tissue adjacent to carcinoma （t = 4.138， P = 0.009）， si-MALAT1 knocked down the expression level of MALAT1 obviously. After knockdown of MALAT1， the proliferation of sw480 and sw620 cell was slowed down （t = 2.957， P = 0.009； t = 1.936， P = 0.017）， and they were more sensitive for 5-FU and Oxaliplatin. After decreasing the level of MALAT1， the levels of P13K and p-AKT were decreased， while the level of AKT had no significant difference. Conclusion MALAT1 plays an important role in proliferation and chemotherapy resistance of colorectal cancer， which may be a potential therapeutic target for the treatment of colorectal cancer.

[Key words] Colorectal cancer； MALAT1； Chemotherapy； Drug resistance

长链非编码RNA（lncRNA）是一种长度大于200个核苷酸的RNA分子，由于缺乏开放阅读框，lncRNA并不编码蛋白质，而是以RNA的形式在表观遗传学、转录水平和转录后3个层面调控基因表_[1-2]，从而在肿瘤的发生发展及转移等多个过程中发挥重要作用[3-5]。肺腺癌相关转录因子1（metastasis-associated lung adenocarcinoma transcript 1，MALAT1）是最早发现的长链非编码RNA之一，最初发现于人类非小细胞肺癌[6]，在肺癌、膀胱癌、肝癌等多种恶性肿瘤中均呈现异常表达的状态，可以影响肿瘤的发生、侵袭和迁移[7-9]，但是其与肿瘤耐药相关性研究较少，目前仅有研究证实MALAT1可以降低胰腺癌细胞的化疗敏感性。本研究拟观察MALAT1对于结直肠癌细胞增殖及化疗药物应答的影响，并对相关机制进行初步探讨。