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MALAT1 调节黑色素瘤细胞中的 miR-34a 表达。

MALAT1 regulates miR-34a expression in melanoma cells.

机构信息

Department of Dermatology, Air Force Medical Center, PLA, Beijing, China.

Department of Radiation Oncology, Air Force Medical Center, PLA, Beijing, China.

出版信息

Cell Death Dis. 2019 May 17;10(6):389. doi: 10.1038/s41419-019-1620-3.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9905/6525244/3db07f922f75/41419_2019_1620_Fig1_HTML.jpg

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