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长链非编码 RNA MALAT1 在癌症中的诊断、预后和治疗意义。

Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer.

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

出版信息

Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188502. doi: 10.1016/j.bbcan.2021.188502. Epub 2021 Jan 8.

Abstract

Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is a widely studied lncRNA in cancer. Although dispensable for normal physiology, MALAT1 is important for cancer-related pathways regulation. It is localized in the nuclear speckles periphery along with centrally located pre-RNA splicing factors. MALAT1 associated cancer signaling pathways include MAPK/ERK, PI3K/AKT, β-catenin/Wnt, Hippo, VEGF, YAP, etc. Molecular tools such as immunoprecipitation, RNA pull-down, reporter assay, Northern blotting, microarray, and q-RT-PCR has been used to elucidate MALAT1's function in cancer pathogenesis. MALAT1 can regulate multiple steps in the development of tumours. The diagnostic and prognostic significance of MALAT1 has been demonstrated in cancers of the breast, cervix, colorectum, gallbladder, lung, ovary, pancreas, prostate, glioma, hepatocellular carcinoma, and multiple myeloma. MALAT1 has also emerged as a novel therapeutic target for solid as well as hematological malignancies. In experimental models, siRNA and antisense oligonucleotide (ASO) based strategy has been used for targeting MALAT1. The lncRNA has also been targeted for the chemosensitization and radiosensitization of cancer cells. However, most studies have been performed in preclinical models. How the cross-talk of MALAT1 with other signaling pathways affect cancer pathogenesis is the focus of this article. The diagnostic, prognostic, and therapeutic significance of MALAT1 in multiple cancer types are discussed.

摘要

转移相关肺腺癌转录物 1(MALAT1)是癌症中研究广泛的 lncRNA。尽管 MALAT1 对于正常生理过程不是必需的,但它对于癌症相关途径的调节很重要。它位于核斑点的外周,与中央定位的前 RNA 剪接因子一起。MALAT1 相关的癌症信号通路包括 MAPK/ERK、PI3K/AKT、β-catenin/Wnt、Hippo、VEGF、YAP 等。免疫沉淀、RNA 下拉、报告基因检测、Northern 印迹、微阵列和 q-RT-PCR 等分子工具已被用于阐明 MALAT1 在癌症发病机制中的作用。MALAT1 可以调节肿瘤发生的多个步骤。MALAT1 的诊断和预后意义已在乳腺癌、宫颈癌、结直肠癌、胆囊癌、肺癌、卵巢癌、胰腺癌、前列腺癌、神经胶质瘤、肝细胞癌和多发性骨髓瘤等癌症中得到证实。MALAT1 也已成为实体瘤和血液恶性肿瘤的新治疗靶点。在实验模型中,已使用 siRNA 和反义寡核苷酸(ASO)策略来靶向 MALAT1。该 lncRNA 还被用于癌症细胞的化疗增敏和放疗增敏。然而,大多数研究都是在临床前模型中进行的。MALAT1 与其他信号通路的相互作用如何影响癌症发病机制是本文的重点。讨论了 MALAT1 在多种癌症类型中的诊断、预后和治疗意义。

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