长链非编码RNA LINC01105调控肝癌对胸腺素α1耐药  

Regulation of thymosin α1 resistance to hepatocellular carcinoma by long chain non-coding RNA LINC01105

作　　者：黄凤霞 李海燕 李正堃 黄君华 雷燕[2] HUANG Fengxia;LI Haiyan;LI Zhengkun;HUANG Junhua;LEI Yan(Department of Medical Technology Clinical,Xi’an Medical University,Xi'an 710021,China)

机构地区：[1]西安医学院医学技术学院,西安710021 [2]川北医学院附属医院检验科,南充637000

出　　处：《中国免疫学杂志》2022年第10期1207-1211,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金青年项目(81700546);西安医学院2020年校级大学生创新创业训练计划项目(121520091);临床分子诊断学重点学科(0114-122011907)资助。

摘　　要：目的:初步探究长链非编码RNA LINC01105调控肝癌对胸腺素α1耐药的机制。方法:qRT-PCR检测肝细胞癌(HCC)组织和细胞LINC01105和miR-6769b-5p表达;荧光素酶报告实验检测LINC01105和miR-6769b-5p的靶向关系;qRT-PCR检测敲低LINC01105后miR-6769b-5p表达;CCK-8检测敲低LINC01105和miR-6769b-5p后不同浓度胸腺素α1处理下HCC细胞存活率;流式细胞术检测敲低LINC01105和miR-6769b-5p后,胸腺素α1处理下HCC细胞周期分布情况;构建小鼠肝癌异种移植模型,检测小鼠体内LINC01105和miR-6769b-5p调控对胸腺素α对HCC敏感性的影响。结果:HCC组织和细胞中LINC01105均呈高表达,而miR-6769b-5p均呈低表达;LINC01105可靶向抑制miR-6769b-5p mRNA表达;敲低LINC01105或过表达miR-6769b-5p可促进HCC对胸腺素α1的敏感性,并阻滞HCC细胞由S期进入G1期,而敲低LINC01105后抑制miR-6769b-5p表达,HCC细胞对胸腺素α1的敏感性恢复,HCC细胞S期到G1期阻滞也有所恢复;敲低小鼠LINC01105或过表达miR-6769b-5p均可显著增强HCC对胸腺素α1的敏感度,而敲低LINC01105同时抑制miR-6769b-5p表达,HCC对胸腺素α1的敏感度略有恢复。结论:LINC01105可通过抑制miR-6769b-5p表达促进肝癌对胸腺素α1的耐药性。Objective:To preliminarily explore mechanism of long-chain non-coding RNA LINC01105 regulates thymosin α1resistance in liver cancer.Methods:qRT-PCR was used to detect expressions of LINC01105 and miR-6769b-5p in hepatocellular carcinoma(HCC)tissues and cells;luciferase reporter assay to detect targeting relationship of LINC01105 and miR-6769b-5p;qRT-PCR to detect expression of miR-6769b-5p after knockdown of LINC01105;CCK-8 assay to detect survival rate of HCC cells under different concentrations of thymosin α1 treatment after knockdown of LINC01105 and miR-6769b-5p;flow cytometry to detect distribution of cell cycle after knockdown of LINC01105 and miR-6769b-5p under thymosin α1 treatment.Xenograft mice model of liver cancer was constructed,and sensitivity of HCC to thymosin α1 of LINC01105 and miR-6769b-5p regulating in vivo was measured.Results:LINC01105 was highly expressed in both HCC tissues and cells,while miR-6769b-5p was lowly expressed;LINC01105could targeting inhibit expression of miR-6769b-5p mRNA;knockdown LINC01105 or over-expressing of miR-6769b-5p could promote sensitivity of HCC to thymosin α1 and arrest HCC cells from S phase into G1phase,while knockdown of LINC01105 inhibited miR-6769b-5p expression,sensitivity of HCC cells to thymosin α1 was recovered,and arrest of HCC cells from S phase to G1phase was also recovered;knockdown of LINC01105 or over-expressing of miR-6769b-5p could increase sensitivity of HCC to thymosin α1in mice,while knockdown of LINC01105 inhibited miR-6769b-5p expression and slightly restored sensitivity of HCC to thymosin α1.Conclusion:LINC01105 could promote resistance of liver cancer to thymosin α1 by inhibiting miR-6769b-5p.

关 键 词：LINC00511 miR-6769b-5p 肝细胞癌 胸腺素Α1 耐药 

分 类 号：R735.7[医药卫生—肿瘤]