Feng Yimin, Wu Fengjuan, Wu Yuanning, Guo Zihan, Ji Xiang
Department of Clinical Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong 250033, China.
Department of Pulmonary and Critical Care Medicine, Heze Municipal Hospital, Heze, Shandong 274031, China.
Transl Oncol. 2023 Jun;32:101661. doi: 10.1016/j.tranon.2023.101661. Epub 2023 Apr 8.
N6-methyladenosine (m6A) modification plays key roles in tumor progression. LncRNA deoxyguanosine kinase antisense RNA 1 (DGUOK-AS1) has been reported as a promoter in tumors, but its role and mechanism in non-small cell lung cancer (NSCLC) development remain uncertain.
Cell proliferation, migration, invasion and angiogenesis were investigated via CCK-8, colony formation, transwell, and tube formation assays, respectively. The location of DGUOK-AS1 was detected via FISH assay. The interaction relationship among DGUOK-AS1, IGF2BP2 and TRPM7 was confirmed by RIP and MeRIP assays. The effects of DGUOK-AS1 on NSCLC growth and metastasis in vivo were investigated using xenograft and pulmonary metastatic models.
DGUOK-AS1 was upregulated in NSCLC. DGUOK-AS1 silencing inhibited NSCLC cell proliferation, migration, invasion and angiogenesis. DGUOK-AS1 was mostly expressed in cytoplasm, and positively regulated IGF2BP2. METTL3/IGF2BP2 axis could increase TRPM7 mRNA stability in m6A-dependent manner. TRPM7 overexpression reversed the inhibitive function of DGUOK-AS1 silencing on NSCLC development. DGUOK-AS1 knockdown suppressed NSCLC cell growth and metastasis in nude mice.
DGUOK-AS1 silencing restrains NSCLC cell growth and metastasis through decreasing TRPM7 stability via regulation of the METTL3/IGF2BP2-mediated m6A modification.
N6-甲基腺苷（m6A）修饰在肿瘤进展中起关键作用。长链非编码RNA脱氧鸟苷激酶反义RNA 1（DGUOK-AS1）已被报道为肿瘤中的一个促进因子，但其在非小细胞肺癌（NSCLC）发生发展中的作用及机制仍不明确。
分别通过CCK-8、集落形成、Transwell和管腔形成实验研究细胞增殖、迁移、侵袭和血管生成。通过荧光原位杂交（FISH）实验检测DGUOK-AS1的定位。通过RNA免疫沉淀（RIP）和甲基化RNA免疫沉淀（MeRIP）实验证实DGUOK-AS1、胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）和瞬时受体电位阳离子通道M7（TRPM7）之间的相互作用关系。使用异种移植和肺转移模型研究DGUOK-AS1对NSCLC体内生长和转移的影响。
DGUOK-AS1在NSCLC中上调。DGUOK-AS1沉默抑制NSCLC细胞增殖、迁移、侵袭和血管生成。DGUOK-AS1主要在细胞质中表达，并正向调节IGF2BP2。甲基转移酶样3（METTL3）/IGF2BP2轴可以以m6A依赖的方式增加TRPM7 mRNA的稳定性。TRPM7过表达逆转了DGUOK-AS1沉默对NSCLC发展的抑制作用。DGUOK-AS1敲低抑制了裸鼠体内NSCLC细胞的生长和转移。
DGUOK-AS1沉默通过调控METTL3/IGF2BP2介导的m6A修饰降低TRPM7稳定性，从而抑制NSCLC细胞生长和转移。
