Qiu Haijiang, Chen Fangchao, Chen Minjun
Department of Rheumatology & Immunology, the Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou 510641, China
Department of Rheumatology & Immunology, the Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou 510641, China.
Biol Open. 2019 Aug 1;8(8):bio042937. doi: 10.1242/bio.042937.
Melanoma with rapid progression towards metastasis has become the deadliest form of skin cancer. However, the mechanism of melanoma growth and metastasis is still unclear. Here, we found that miRNA-138 was lowly expressed and hypoxia-inducible factor 1α (HIF1α) was highly expressed in patients' melanoma tissue compared with the paracancerous tissues, and they had a significant negative correlation (r=-0.877, <0.001). Patients with miRNA-138/HIF1α signatures were predominant in late stage III/IV of melanoma. Further, bioinformatic analysis demonstrated that miRNA-138 directly targeted HIF1α. We found that the introduction of pre-miRNA-138 sequences to A375 cells reduced HIF1α mRNA expression and suppressed cell proliferation, migration and invasion. Overexpression of miRNA-138 or inhibition of HIF1α significantly suppressed the growth and metastasis of melanoma Our study demonstrates the role and clinical relevance of miRNA-138 and HIF1α in melanoma cell growth and metastasis, providing a novel therapeutic target for suppression of melanoma growth and metastasis.
迅速进展至转移的黑色素瘤已成为最致命的皮肤癌形式。然而，黑色素瘤生长和转移的机制仍不清楚。在此，我们发现与癌旁组织相比，miRNA - 138在患者黑色素瘤组织中低表达，而缺氧诱导因子1α（HIF1α）高表达，且二者呈显著负相关（r = - 0.877，<0.001）。具有miRNA - 138/HIF1α特征的患者在黑色素瘤晚期III/IV期占主导。此外，生物信息学分析表明miRNA - 138直接靶向HIF1α。我们发现将pre - miRNA - 138序列导入A375细胞可降低HIF1α mRNA表达，并抑制细胞增殖、迁移和侵袭。miRNA - 138的过表达或HIF1α的抑制均显著抑制黑色素瘤的生长和转移。我们的研究证明了miRNA - 138和HIF1α在黑色素瘤细胞生长和转移中的作用及临床相关性，为抑制黑色素瘤生长和转移提供了新的治疗靶点。
