沉默长链非编码RNA FAM83H-AS1提高肺腺癌细胞的化学治疗敏感性  

Silencing of long noncoding RNA FAM83H-AS1 enhances chemosensitivity of lung adenocarcinoma cells

作　　者：郭家辰[1] 徐然[2] GUO Jiachen;XU Ran(Department of Clinical Laboratory,Shengjing Hospital of China Medical University,Shenyang 110004,China;Department of Thoracic Surgery,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院检验科,沈阳110004 [2]中国医科大学附属盛京医院胸外科,沈阳110004

出　　处：《中国医科大学学报》2022年第3期216-220,225,共6页Journal of China Medical University

基　　金：辽宁省自然科学基金(2021-MS-202);辽宁省博士科研启动基金(201601121)。

摘　　要：目的探讨长链非编码RNA FAM83H-AS1调控肺腺癌细胞化学治疗(简称化疗)敏感性(培美曲塞和顺铂)的作用效果及机制。方法实时定量PCR法检测FAM83H-AS1在肺腺癌组织和细胞系中的表达。CCK8法检测并计算肺腺癌细胞对培美曲塞和顺铂的半抑制率(IC50)。基于TCGA数据库,应用生物信息学方法分析FAM83H-AS1与ATP结合盒亚家族C成员1(ABCC1)基因表达的相关性。Western boltting检测ABCC1蛋白的表达。结果与癌旁正常肺组织和人肺泡上皮细胞相比,FAM83H-AS1在肺腺癌组织和细胞系(PC9和A549)中高表达。FAM83H-AS1的表达与肺腺癌患者的吸烟史和化疗不敏感呈正相关。与化疗敏感的肺腺癌组织和细胞系(A549)相比,FAM83H-AS1在化疗(培美曲塞和顺铂)耐药的肺腺癌组织和细胞系(A549/CR)中高表达。沉默FAM83H-AS1能够降低A549/CR细胞对培美曲塞和顺铂的IC50,提高对化疗药物的敏感性。在肺腺癌中FAM83H-AS1与多药耐药相关基因ABCC1的表达呈正相关。沉默FAM83H-AS1能够降低A549/CR细胞中ABCC1蛋白的表达。结论FAM83H-AS1在肺腺癌中高表达,且与肺腺癌的化疗不敏感相关,沉默FAM83H-AS1通过下调ABCC1蛋白的表达提高肺腺癌细胞对培美曲塞和顺铂的敏感性。Objective To investigate the effect and mechanism of long noncoding RNA FAM83H-AS1 on the sensitivity of lung adenocarcinoma(LUAD)cells to pemetrexed and cisplatin.Methods The expression of FAM83H-AS1 in LUAD tissues and cell line was detected by real-time quantitative PCR.The half-inhibitory concentration(IC50)of pemetrexed and cisplatin was measured and calculated by the enhanced CCK8 method.TCGA database bioinformatics analysis explored the correlation between FAM83H-AS1 and ABCC1 gene expression.The expression of ABBC1 protein was detected by Western blotting.Results FAM83H-AS1 was highly expressed in LUAD tissues and PC9 and A549 cell lines compared with normal lung tissues and human alveolar epithelial cells.The expression of FAM83H-AS1 was positively correlated with smoking history and insensitivity to chemotherapy in LUAD patients.FAM83H-AS1 was highly expressed in pemetrexed and cisplatin-resistant LUAD tissues and cell lines(A549/CR)compared with sensitive neoadjuvant chemotherapy LUAD tissues and cell lines(A549).Silencing of FAM83H-AS1 reduced the IC50 of pemetrexed and cisplatin in A549 cells and improved the sensitivity to chemotherapy drugs.FAM83H-AS1 was positively correlated with the expression of multidrug resistance related protein ABCC1 in LUAD.Silencing of FAM83H-AS1 down-regulated ABCC1 expression in A549/CR cells.Conclusion FAM83H-AS1 was highly expressed in LUAD and was positively correlated with insensitivity to neoadjuvant chemotherapy in LUAD patients.Silencing FAM83H-AS1 enhances the chemosensitivity of LUAD cells to pemetrexed and cisplatin by inhibiting the expression of ABCC1 protein.

关 键 词：肺腺癌 FAM83H-AS1 化学治疗 ATP结合盒亚家族C成员1 

分 类 号：R734[医药卫生—肿瘤]