Department of Thoracic Surgery, The People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, PR China.
The Cardiothoracic Surgery of Weifang Yidu Central Hospital, Weifang, 262500, Shandong, PR China.
Biomed Pharmacother. 2020 Sep;129:110217. doi: 10.1016/j.biopha.2020.110217. Epub 2020 Jun 16.
As the most common subtype of lung cancer, lung adenocarcinoma (LUAD) is the frequently occurred cancers in human. Therefore, thorough investigation is necessary for understanding the progression of LUAD. HMMR has functioned as a regulator in some cancers, whereas its biological role still needs to be investigated in LUAD. By bioinformatics analysis, we found that HMMR was highly expressed in LUAD tissues and associated with patients' poor prognosis. Further, qRT-PCR demonstrated that HMMR was up-regulated in LUAD tissues and cells. Loss-of-function assays manifested that HMMR knockdown refrained cell proliferation, migration and invasion and enhanced cell apoptosis in LUAD. Later, HMMR was identified as a target gene of miR-34a-5p, which expressed at a low level in LUAD cell and played an anti-oncogenic role in LUAD. Simultaneously, we discovered that miR-34a-5p could directly bind to HCG18. Subsequent assays revealed that HCG18 mediated HMMR expression by sequestering miR-34a-5p. At last, rescue assays proved the carcinogenic role of HCG18/miR-34a-5p/HMMR axis in LUAD cells growth. Importantly, HCG18 was found to facilitate tumor growth in LUAD. Conclusively, HCG18 acted an oncogene in LUAD and enhanced LUAD progression by targeting miR-34a-5p/HMMR axis.
作为最常见的肺癌亚型，肺腺癌（LUAD）是人类中常见的癌症。因此，深入研究对于了解 LUAD 的进展是必要的。HMMR 在一些癌症中作为调节剂发挥作用，但其在 LUAD 中的生物学作用仍需要研究。通过生物信息学分析，我们发现 HMMR 在 LUAD 组织中高表达，并与患者的不良预后相关。进一步的 qRT-PCR 表明 HMMR 在 LUAD 组织和细胞中上调。功能丧失实验表明 HMMR 敲低抑制 LUAD 细胞的增殖、迁移和侵袭，并促进细胞凋亡。随后，HMMR 被鉴定为 miR-34a-5p 的靶基因，miR-34a-5p 在 LUAD 细胞中低表达，在 LUAD 中发挥抑癌作用。同时，我们发现 miR-34a-5p 可以直接与 HCG18 结合。后续的实验表明，HCG18 通过隔离 miR-34a-5p 来介导 HMMR 的表达。最后，挽救实验证明了 HCG18/miR-34a-5p/HMMR 轴在 LUAD 细胞生长中的致癌作用。重要的是，HCG18 被发现促进 LUAD 中的肿瘤生长。总之，HCG18 在 LUAD 中起癌基因作用，并通过靶向 miR-34a-5p/HMMR 轴增强 LUAD 的进展。
