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RNA N6 -甲基腺苷修饰酶 HNRNPA2B1 参与非小细胞肺癌的发生发展。

The RNA N -methyladenosine modulator HNRNPA2B1 is involved in the development of non-small cell lung cancer.

机构信息

Department of Thoracic Surgery, Xiamen University Institute of Chest and Lung Disease, Xiang'an Hospital of Xiamen University, Xiamen, China.

出版信息

Clin Exp Pharmacol Physiol. 2022 Mar;49(3):329-340. doi: 10.1111/1440-1681.13608. Epub 2021 Nov 14.

Abstract

The key N  methyladenosine (m A) RNA methylation regulator is associated with multiple tumour progression. However, the m A-associated regulators that influence non-small cell lung cancer (NSCLC) development have not been fully clarified. The m A regulator expression pattern of NSCLC patients from The Cancer Genome Atlas (TCGA) dataset was identified. Aberrations of m6A modulators are related to NSCLC development via cBioPortal database. Furthermore, we found that IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO are significantly correlated with advanced stage disease or clinical outcomes in NSCLC by UALCAN and Kaplan-Meier plot. Bioinformatics analysis showed that m A modulators (IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO) are associated with immunomodulator and immune infiltration expression in NSCLC via the Tumor Immune Estimation Resource (TIMER) database. The co-expression between these m6A-associated modulators was analysed by protein-protein interaction networks. Finally, we found that HNRNPA2B1 promotes NSCLC development in vitro by regulating cell proliferation and metastasis functions via Cell Counting Kit 8 (CCK8) and transwell assay. Our study showed that HNRNPA2B1 is a promising target and biomarker for cancer therapy in NSCLC.

摘要

关键的 N 6-甲基腺苷(m A)RNA 甲基化调节剂与多种肿瘤进展有关。然而,影响非小细胞肺癌(NSCLC)发展的 m A 相关调节剂尚未完全阐明。从癌症基因组图谱(TCGA)数据库中确定了 NSCLC 患者的 m A 调节剂表达模式。通过 cBioPortal 数据库,m6A 调节剂的异常与 NSCLC 的发生有关。此外,我们通过 UALCAN 和 Kaplan-Meier 绘图发现,IGF2BP2、IGF2BP3、HNRNPA2B1 和 FTO 在 NSCLC 中与晚期疾病或临床结局显著相关。生物信息学分析表明,m A 调节剂(IGF2BP2、IGF2BP3、HNRNPA2B1 和 FTO)通过肿瘤免疫估计资源(TIMER)数据库与 NSCLC 中的免疫调节剂和免疫浸润表达相关。通过蛋白质-蛋白质相互作用网络分析这些 m6A 相关调节剂之间的共表达。最后,我们发现 HNRNPA2B1 通过调节细胞增殖和转移功能,通过细胞计数试剂盒 8(CCK8)和 Transwell 测定在体外促进 NSCLC 的发展。我们的研究表明,HNRNPA2B1 是 NSCLC 癌症治疗有前途的靶点和生物标志物。

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