Department of Dermatology, Air Force Medical Center, PLA, Beijing, China.
Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, China.
Cell Death Dis. 2019 May 17;10(6):389. doi: 10.1038/s41419-019-1620-3.
Melanoma is one of the most common skin malignancies. Both microRNAs and long non-coding RNAs (lncRNAs) have critical roles in the progression of cancers, including melanoma. However, the underlying molecular mechanism has not been fully characterized. We demonstrated that miR-34a is negatively correlated with MALAT1 in melanoma cells and tumor specimens. Interestingly, MALAT1, which contains functional sequence-specific miR-34a-binding sites, regulates miR-34a stability in melanoma cells and in vivo. Importantly, MALAT1 was significantly enriched in the Ago2 complex, but not when the MALAT1-binding site of miR-34a was mutated. Furthermore, MALAT1 could be shown to regulate c-Myc and Met expression by functioning as a miR-34a sponge. Our results reveal an unexpected mode of action for MALAT1 as an important regulator of miR-34a.
黑色素瘤是最常见的皮肤恶性肿瘤之一。microRNAs 和长链非编码 RNA(lncRNAs)在癌症的进展中都起着关键作用,包括黑色素瘤。然而,其潜在的分子机制尚未完全阐明。我们证实 miR-34a 在黑色素瘤细胞和肿瘤标本中与 MALAT1 呈负相关。有趣的是,含有功能序列特异性 miR-34a 结合位点的 MALAT1 调节黑色素瘤细胞和体内 miR-34a 的稳定性。重要的是,MALAT1 在 Ago2 复合物中显著富集,但当 miR-34a 的 MALAT1 结合位点发生突变时则不然。此外,MALAT1 可作为 miR-34a 的海绵,通过调节 c-Myc 和 Met 的表达。我们的研究结果揭示了 MALAT1 作为 miR-34a 重要调节因子的一种意想不到的作用模式。