Hubrecht Institute, University Medical Center Utrecht, Cancer Genomics Center, Utrecht, The Netherlands.
PLoS One. 2012;7(8):e43569. doi: 10.1371/journal.pone.0043569. Epub 2012 Aug 22.
Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs) with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.
恶性黑色素瘤是一种预后不良的侵袭性皮肤癌。尽管人们对这种疾病的认识和预防有所提高，但它的发病率仍在迅速上升。 microRNAs（miRNAs）是一类通过与部分互补的靶位点抑制信使 RNA（mRNA）来调节细胞过程的小 RNA 分子。已经有研究表明，几种 miRNAs 可以通过限制增殖、侵袭性、肿瘤血管生成和干性来减弱癌症表型。在这里，我们采用了一种全基因组规模的慢病毒人 miRNA 表达文库，系统地研究了哪些 miRNA 能够降低 A375 黑色素瘤细胞的活力。我们强调了对黑色素瘤细胞增殖抑制作用最强的抑制剂，包括 miR-15/16、miR-141/200a 和 miR-96/182 家族的 miRNAs 和 miR-203。这些 miRNAs 的异位表达导致体外和体内黑色素瘤细胞的长期扩张受到抑制。我们特别表明，当作为几种黑色素瘤细胞系中的合成 miRNA 引入时，miR-16、miR-497、miR-96 和 miR-182 是有效的效应物。我们的研究对干扰黑色素瘤细胞增殖和活力的 miRNAs 进行了全面研究，并提供了一组特别有希望应用于黑色素瘤治疗的 miRNAs。
