lncRNA MALAT1调控人肝胆管癌细胞侵袭及凋亡影响胆管癌发生发展临床研究

肝癌电子杂志 ›› 2021, Vol. 8 ›› Issue (2): 26-32.

lncRNA MALAT1调控人肝胆管癌细胞侵袭及凋亡影响胆管癌发生发展临床研究

魏志成¹, 马腾¹, 车旭^1,2, 赵宏^3,*

1.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院深圳医院肝胆外科,广东深圳 518116;
2.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院胰胃外科,北京 100021;
3.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院肝胆外科,北京 100021

收稿日期:2021-03-29 发布日期:2021-07-16
通讯作者: *赵宏,E-mail: pumczhaohong@126.com
作者简介:魏志成, 主治医师,国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院,肿瘤医院深圳医院肝胆外科
基金资助:
深圳市“医疗卫生三名工程”项目资助（SZS M202011010）

lncRNA MALAT1 impacts cholangiocarcinoma initiation and development by regulating RBE cell invasion and apoptosis

Wei Zhicheng¹, Ma Teng¹, Che Xu^1,2, Zhao Hong^3,*

1. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong, China;
2. Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China;
3. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Received:2021-03-29 Published:2021-07-16

摘要/Abstract

摘要： 目的: 探究肺腺癌转移相关转录物1（metastasis associated in lung denocarcinoma transcript 1,MALAT1）调控肝内胆管细胞癌（intrahepatic cholangiocarcinoma, ICC）体外细胞侵袭、迁移及凋亡和体内细胞增殖,并参与ICC的发生发展的机制。方法: 利用GeneCards和LncExpDB数据库发现MALAT1基本信息;qRT-PCR和原位杂交FISH检测MALAT1在27例ICC患者组织中的表达情况;Tranwell、细胞划痕及Tunel细胞凋亡检测MALAT1对人肝胆管癌细胞系(RBE细胞系）侵袭、迁移及凋亡情况;原位杂交FISH和PCNA免疫组织化学及Ki67免疫荧光实验检测MALAT1在皮下肿瘤组织中荧光探针信号与体内细胞增殖情况。结果: MALAT1定位于 11p13.1,转录本长8708bp,在各类肿瘤和疾病中有不同程度的表达差异;MALAT1在27例ICC患者组织中均上调; MALAT1促进RBE侵袭、迁移及抑制凋亡,而敲低MALAT1则促进凋亡; MALAT1在皮下肿瘤组织中的阳性表达显著增加;过表达MALAT1促进体内细胞增殖,敲低MALAT1则抑制体内细胞增殖。结论: MALAT1作为ICC一种潜在标志物,通过调控干扰MALAT1的表达可能为ICC的诊断和治疗提供新的研究方向。

关键词: 胆管细胞癌, 肺腺癌转移相关转录物1, 小干扰RNA, 人肝胆管癌细胞

Abstract: Objective: This study aims to explore that metastasis associated in lung denocarcinoma transcript 1(MALAT1)participates in intrahepatic cholangiocarcinoma (ICC) initiation and development via regulating cell invasion, migration, apoptosis in vitro and cell proliferation in vivo. Methods: GeneCards and LncExpDB database were used to reveal basic information of MALAT1. qRT-PCR and FISH were used to detect MALAT1 expression in 27 cases of ICC. Tranwell, Cell wound scratch and Tunel cell apoptosis were used to detect impacts of MALAT1 on RBE cell invasion, migration and apoptosis. FISH, PCNA immunohistochemistry and Ki67 Immunofluorescence were used to detect fluorescent probe signal of MALAT1 in subcutaneous tumor tissues and the cell proliferation in vivo. Results: MALAT1 located in 11p13.1 with a length of 8708bp in transcript, showing different expression in multiple tumors and diseases. MALAT1 was up-regulated in 27 cases of ICC. MALAT1 promoted RBE cell invasion, migration and inhibited apoptosis, while knockdown of MALAT1 could facilitate apoptosis. Positive expression of MALAT1 in subcutaneous tumor tissues was obviously increased. Over-expression MALAT1 could promote in vivo cell proliferation, whereas knockdown of MALAT1 could inhibit in vivo cell proliferation. Conclusion: MALAT1 could serve as a potential maker in ICC, and siMALAT1 provides new studying directions for cholangiocarcinoma diagnosis and therapies.

Key words: Cholangiocarcinoma, Metastasis associated in lung denocarcinoma transcript 1, Small interfering RNA, Human bile duct carcinoma cell

魏志成, 马腾, 车旭, 赵宏. lncRNA MALAT1调控人肝胆管癌细胞侵袭及凋亡影响胆管癌发生发展临床研究[J]. 肝癌电子杂志, 2021, 8(2): 26-32.

Wei Zhicheng, Ma Teng, Che Xu, Zhao Hong. lncRNA MALAT1 impacts cholangiocarcinoma initiation and development by regulating RBE cell invasion and apoptosis[J]. Electronic Journal of Liver Tumor, 2021, 8(2): 26-32.

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