LncRNA SNHG15 regulates EGFR-TKI acquired resistance in lung adenocarcinoma through sponging miR-451 to upregulate MDR-1
LncRNA SNHG15 regulates EGFR-TKI acquired resistance in lung adenocarcinoma through sponging miR-451 to upregulate MDR-1
复制标题
LncRNA SNHG15通过海绵miR-451上调MDR-1来调节肺腺癌中EGFR-TKI获得性耐药
DOI：
10.1038/s41419-020-2683-x
复制
发表时间：
2020-07-13
影响因子：
9
通讯作者：
Feng, Jifeng
中科院分区：
文献类型：
--
作者：
Huang, Jiayuan;Pan, Banzhou;Feng, Jifeng
肺腺癌（LUAD）是非小细胞肺癌（NSCLC）的主要组成部分，在全球范围内引起了极大的健康问题。LUAD治疗的重中之重是应对吉非替尼耐药。长的非编码RNA被证明在肿瘤恶化过程中修饰吉非替尼抗性。该研究的重点是解决小核仁RNA宿主基因15（SNHG 15）在LUAD中修饰吉非替尼耐药性的功能。此前，NOTCH途径与LUAD化疗耐药性有关。在A549/GR和H1975/GR细胞中，在NOTCH-1耗尽后SNHG 15水平升高。功能研究表明SNHG 15和多药耐药蛋白1（MDR-1）在吉非替尼耐药的LUAD细胞中过表达并具有促肿瘤作用，而miR-451在吉非替尼耐药的LUAD细胞中下调并具有抑肿瘤作用。SNHG 15在GR LUAD细胞中以胞质形式分布。此外，SNHG 15从miR-451的抑制中释放MDR-1，导致MDR-1的促进。此外，SNHG 15的升高可能归因于ZEB 1。挽救试验强调，下游分子MDR-1和miR-451可以逆转SNHG 15下调对吉非替尼耐药LUAD细胞的影响。SNHG 15可通过调控miR-451/MDR-1改变LUAD细胞对吉非替尼的耐药性，这可能为LUAD的化疗提供新的思路。
Lung adenocarcinoma (LUAD) is the main component of non-small-cell lung cancer (NSCLC) and causes a great health concern globally. The top priority of LUAD treatment is to deal with gefitinib resistance. Long non-coding RNAs are certified to modify gefitinib resistance in the course of tumor aggravation. The study focuses on addressing the function of small nucleolar RNA host gene 15 (SNHG15) on modifying gefitinib resistance in LUAD. Previously, NOTCH pathway is implicated in LUAD chemo-resistance. SNHG15 level was boosted following the depletion of NOTCH-1 in A549/GR and H1975/GR cells. Functional studies indicated that SNHG15 and multidrug resistance protein 1 (MDR-1) were overexpressed and possess tumor-promoting functions in gefitinib-resistant LUAD cells while miR-451 was downregulated and possess tumor-suppressive behaviors in gefitinib-resistant LUAD cells. Mechanically, the SNHG15 was cytoplasmically distributed in GR LUAD cells. In addition, SNHG15 released MDR-1 from the suppression of miR-451, leading to MDR-1 promotion. In addition, the elevation of SNHG15 could be attributed to ZEB1. Rescue assays highlighted that downstream molecules MDR-1 and miR-451 could reverse the effects of SNHG15 downregulation on gefitinib-resistant LUAD cells. SNHG15 could alter chemo-resistance of LUAD cells to Gefitinib via regulating miR-451/MDR-1, which could be inspiring findings for the advancement of chemo-therapies for LUAD.