Farooqi Ammad Ahmad, Legaki Evangelia, Gazouli Maria, Rinaldi Silvia, Berardi Rossana
Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 54000. Pakistan.
Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens,. Greece.
Curr Cancer Drug Targets. 2020 Jul 30. doi: 10.2174/1568009620999200730183110.
The central dogma of molecular biology, has remained a cornerstone of classical molecular biology. However, serendipitously discovered microRNAs (miRNAs) in nematodes paradigmatically shifted our current knowledge of the intricate mechanisms during transitions from transcription to translation. The discovery of miRNA captured considerable attention and appreciation, and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets that are regulated by MALAT1 to stimulate or repress the expression of target genes. However, in this review, our main focus is to summarize mechanistic insights on MALAT1-mediated regulation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening. However, there is still a need to identify additional mechanisms. MALAT1 is involved in the multi-layered regulation of multiple transduction cascades, and detailed analysis of different pathways will be advantageous in getting a step closer to individualized medicine.
分子生物学的中心法则一直是经典分子生物学的基石。然而,线虫中意外发现的微小RNA(miRNA)范式性地改变了我们目前对从转录到翻译过程中复杂机制的认识。miRNA的发现引起了广泛关注和赞赏,我们见证了非编码RNA领域的爆发式发展。非编码RNA领域的突破性发现有助于更好地表征微小RNA和长链非编码RNA(LncRNA)。受MALAT1调控以刺激或抑制靶基因表达的miRNA靶标越来越多。然而,在本综述中,我们的主要重点是总结关于MALAT1介导的致癌信号通路调控的机制见解。我们讨论了MALAT1如何在各种癌症中调节TGF/SMAD和Hippo通路。我们还全面总结了JAK/STAT和Wnt/β-连环蛋白通路如何刺激MALAT1表达,以及MALAT1如何增强这些信号级联反应以促进癌症。MALAT1的研究已经有了很大的拓展。然而,仍然需要确定其他机制。MALAT1参与多个转导级联反应的多层调控,对不同通路的详细分析将有助于更接近个性化医疗。