Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong province, China.
Department of Medical Oncology, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong Province, China.
BMC Cancer. 2018 Apr 11;18(1):404. doi: 10.1186/s12885-018-4233-9.
Melanoma is notoriously resistant to all current modalities of cancer therapies including chemotherapy. In recent years, microRNAs (miRNAs) have emerged as molecular regulators in the development and progression of melanoma. However, the relationship between microRNA and chemo-resistance of melanoma is little known. In present study, we aimed to investigate the miRNAs related to cisplatin-resistance in melanoma cells.
After cisplatin (DDP) resistant melanoma cells (M8/DDP and SK-Mel-19/DDP) were established in-vitro, high-throughput screening of differentially expressed miRNAs between resistant cells and parental cells were performed.
It was found that a cancer-related miRNA, miR-30a-5p, was highly over-expressed in resistant cells. Transfection of miR-30a-5p mimic or inhibitor could alter the sensitivity of melanoma cells to cisplatin. Next, we showed that Insulin Like Growth Factor 1 Receptor (IGF1R) gene turned out to be a direct target of miR-30a-5p. Knockdown of IGF1R in melanoma cells could not only reduce the sensitivity to cisplatin but also lead to cell cycle arrest by regulating phosphorylation of Serine-Threonine Protein Kinase (P-AKT (Ser473)) and Tumor Protein P53 (P53).
Taken together, our study demonstrated that miR-30a-5p could influence chemo-resistance by targeting IGF1R gene in melanoma cells, which might provide a potential target for the therapy of chemo-resistant melanoma cells.
黑色素瘤是一种众所周知的对所有当前癌症治疗方法（包括化疗）都具有耐药性的肿瘤。近年来，microRNAs（miRNAs）已成为黑色素瘤发生和发展的分子调节剂。然而，miRNA 与黑色素瘤化疗耐药性之间的关系知之甚少。在本研究中，我们旨在研究与黑色素瘤细胞顺铂耐药相关的 miRNAs。
在体外建立顺铂耐药黑色素瘤细胞（M8/DDP 和 SK-Mel-19/DDP）后，对耐药细胞与亲本细胞之间差异表达的 miRNAs 进行高通量筛选。
研究发现，一种与癌症相关的 miRNA，miR-30a-5p，在耐药细胞中高度过表达。miR-30a-5p 模拟物或抑制剂的转染可改变黑色素瘤细胞对顺铂的敏感性。接下来，我们表明胰岛素样生长因子 1 受体（IGF1R）基因是 miR-30a-5p 的直接靶标。IGF1R 在黑色素瘤细胞中的敲低不仅降低了对顺铂的敏感性，而且通过调节丝氨酸-苏氨酸蛋白激酶（P-AKT（Ser473））和肿瘤蛋白 P53（P53）的磷酸化导致细胞周期停滞。
综上所述，我们的研究表明，miR-30a-5p 可通过靶向黑色素瘤细胞中的 IGF1R 基因影响化疗耐药性，这可能为化疗耐药性黑色素瘤细胞的治疗提供潜在靶点。
