Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.
Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.
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非小细胞肺癌细胞长链非编码RNA PCAT-1表达与吉非替尼耐药的关系
DOI：
10.1186/s12931-021-01719-7
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发表时间：
2021-05-12
影响因子：
5.8
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Wang S;Liu C;Lei Q;Wu Z;Miao X;Zhu D;Yang X;Li N;Tang M;Chen Y;Wang W
吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂，已被用作晚期非小细胞肺癌(NSCLC)的一线治疗药物。然而，在治疗过程中，癌细胞往往对吉非替尼产生耐药性，其机制尚不完全清楚。本研究旨在阐明长非编码RNA(LncRNA)-PCAT-1在非小细胞肺癌细胞吉非替尼耐药中的表达及其作用。在这项研究中，我们验证了PCAT-1在非小细胞肺癌吉非替尼耐药组织或细胞中的差异表达。采用PCAT-1基因敲除、克隆形成、Transwell、流式细胞仪和免疫荧光分析等方法验证PCAT-1与吉非替尼敏感性的相关性。裸鼠荷瘤模型验证了PCAT-1能在体内逆转吉非替尼耐药。然后，使用PI3K/Akt激动剂来验证PCAT-1的可能作用机制。PCAT-1在对吉非替尼耐药的非小细胞肺癌组织和细胞中高表达。PCAT-1基因敲除增强了吉非替尼的敏感性，并诱导了H1299/GR细胞的凋亡。PCAT-1基因敲除减少了肿瘤体积和重量，并在体内逆转了获得性吉非替尼耐药性。PCAT-1基因敲除可抑制H1299/GR细胞AKT和GSK3的磷酸化。PI3K/AKT激动剂逆转了PCAT-1基因敲除介导的Gefitinib对H1299/GR细胞敏感性的增强，PCAT-1基因敲除通过抑制NSCLC中AKT和GSK3的磷酸化来改善对Gefitinib的敏感性。PCAT-1可作为提高吉非替尼临床疗效的潜在靶点。
Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been used as first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, during treatment, cancer cells often develop resistance to gefitinib, the mechanisms of which are not fully understood. This study was designed to elucidate the expression and role of long non-coding RNA (lncRNA)-PCAT-1, a potential biomarker for drug resistance and a therapeutic target for NSCLC, in gefitinib resistance in NSCLC cells. In this study, we verified differential PCAT-1 expression in NSCLC gefitinib-resistant tissues or cells. PCAT-1 knockdown, clone formation, Transwell, flow cytometry, and immunofluorescence assays were used to verify the correlation between PCAT-1 and gefitinib sensitivity. A nude mouse tumor-bearing model verified that PCAT-1 can reverse gefitinib resistance in vivo. Then, a PI3K/Akt agonist was used to verify the possible mechanism of PCAT-1 action. PCAT-1 is highly expressed in gefitinib-resistant NSCLC tissues and cells. PCAT-1 knockdown enhanced gefitinib sensitivity and gefitinib-induced apoptosis in H1299/GR cells. PCAT-1 knockdown reduced tumor volume and weight, and reversed acquired gefitinib resistance in vivo. PCAT-1 knockdown inhibited AKT and GSK3 phosphorylation in H1299/GR cells. A PI3K/AKT agonist reversed PCAT-1 knockdown-mediated enhancement of gefitinib sensitivity in H1299/GR cells PCAT-1 knockdown improves sensitivity to gefitinib by inhibition of AKT and GSK3 phosphorylation in NSCLC. PCAT-1 is as potential target for improving the clinical efficacy of gefitinib.
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影响因子：
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作者：
Lu, Xiyi;Huang, Chenjun;Guo, Renhua
通讯作者：
Guo, Renhua
影响因子：
45.3
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影响因子：
50.3
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通讯作者：
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影响因子：
2.9
作者：
Jin S;He J;Li J;Guo R;Shu Y;Liu P
通讯作者：
Liu P
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作者：
Wheler J;Falchook G;Tsimberidou AM;Hong D;Naing A;Piha-Paul S;Chen SS;Heymach J;Fu S;Stephen B;Fok JY;Janku F;Kurzrock R
通讯作者：
Kurzrock R