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。

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

郭家辰¹, 徐然²

中国医科大学附属盛京医院1. 检验科;
2. 胸外科, 沈阳 110004

收稿日期:2021-07-01出版日期:2022-03-30发布日期:2022-03-16
通讯作者:徐然E-mail:xur2@sj-hospital.org
作者简介:郭家辰(1984-),女,主管技师,本科.
基金资助:辽宁省自然科学基金（2021-MS-202）；辽宁省博士科研启动基金（201601121）


关键词: 肺腺癌, FAM83H-AS1, 化学治疗, ATP结合盒亚家族C成员1
Abstract: 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.
Key words: lung adenocarcinoma, FAM83H-AS1, chemotherapy, ATP binding cassette subfamily C member 1
PDF全文下载地址:

https://journal.cmu.edu.cn/CN/article/downloadArticleFile.do?attachType=PDF&id=2950