CircMYBL1 suppressed acquired resistance to osimertinib in non-small-cell lung cancer

IF 1.4 4区医学 Q4 GENETICS & HEREDITY Cancer Genetics Pub Date : 2024-04-15 DOI:10.1016/j.cancergen.2024.04.001

Yaji Li , Nan Wang , Yutang Huang , Shuai He , Meihua Bao , Chunjie Wen , Lanxiang Wu

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Abstract

Circular RNAs (circRNAs) play an important role in the development of acquired resistance to many anticancer drugs. We developed the Non-Small-Cell Lung Cancer (NSCLC) cell lines with acquired resistance to osimertinib, a third-generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and evaluated the different expression profiles of circRNAs in osimertinib-sensitive and -resistant NSCLC cell lines using RNA sequencing (RNA-Seq). The expression of selected differentially expressed circRNAs was verified using quantitative real-time PCR (qRT-PCR) in paired osimertinib-sensitive and -resistant NSCLC cell lines, and in plasma samples of osimertinib-sensitive and -resistant NSCLC patients. We found that circMYBL1(has_circ_0136924) was downregulated after acquired resistance to osimertinib, inhibiting circMYBL1 expression facilitated the proliferation, migration, and invasion in osimertinib-sensitive NSCLC cells. CircMYBL1 may be a novel molecular biomarker and therapeutic target for osimertinib-resistant NSCLC.

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CircMYBL1抑制非小细胞肺癌患者对奥希替尼的获得性耐药性

环状 RNA（circRNA）在许多抗癌药物获得性耐药性的形成过程中发挥着重要作用。我们开发了对第三代表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKIs）奥西美替尼获得性耐药的非小细胞肺癌（NSCLC）细胞系，并利用 RNA 测序（RNA-Seq）评估了奥西美替尼敏感和耐药 NSCLC 细胞系中循环 RNA 的不同表达谱。在配对的奥希替尼敏感和耐药NSCLC细胞系中，以及在奥希替尼敏感和耐药NSCLC患者的血浆样本中，我们使用定量实时PCR（qRT-PCR）技术验证了部分差异表达的circRNAs的表达情况。我们发现，circMYBL1(has_circ_0136924)在对奥希替尼产生耐药性后被下调，抑制circMYBL1的表达有利于奥希替尼敏感的NSCLC细胞的增殖、迁移和侵袭。circMYBL1可能是奥希替尼耐药NSCLC的新型分子生物标记物和治疗靶点。

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来源期刊

Cancer Genetics ONCOLOGY-GENETICS & HEREDITY

CiteScore

3.20

自引率

5.30%

发文量

167

审稿时长

27 days

期刊介绍： The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor.