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长链非编码RNA和微小RNA作为乳腺癌干细胞干性的关键调节因子

LncRNAs and microRNAs as Essential Regulators of Stemness in Breast Cancer Stem Cells.

作者信息

Flores-Huerta Nadia, Silva-Cázares Macrina B, Arriaga-Pizano Lourdes A, Prieto-Chávez Jessica L, López-Camarillo César

机构信息

Laboratorio de Oncogenómica y Proteómica del Cáncer, Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, 03100 CDMX, Mexico.

Doctorado Institucional en Ingeniería y Ciencias de los Materiales, Universidad Autónoma de San Luis Potosí, 78210 San Luis Potosí, Mexico.

出版信息

Biomolecules. 2021 Mar 3;11(3):380. doi: 10.3390/biom11030380.

Abstract

Breast cancer is an aggressive disease with a high incidence in women worldwide. Two decades ago, a controversial hypothesis was proposed that cancer arises from a subpopulation of "tumor initiating cells" or "cancer stem cells-like" (CSC). Today, CSC are defined as small subset of somatic cancer cells within a tumor with self-renewal properties driven by the aberrant expression of genes involved in the maintenance of a stemness-like phenotype. The understanding of the underlying cellular and molecular mechanisms involved in the maintenance of CSC subpopulation are fundamental in the development and persistence of breast cancer. Nowadays, the hypothesis suggests that genetic and epigenetic alterations give rise to breast cancer stem cells (bCSC), which are responsible for self-renewal, tumor growth, chemoresistance, poor prognosis and low survival in patients. However, the prominence of bCSC, as well as the molecular mechanisms that regulates and promotes the malignant phenotypes, are still poorly understood. The role of non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as oncogenes or tumor suppressor genes has been recently highlighted by a plethora of studies in breast cancer. These ncRNAs positively or negatively impact on different signaling pathways that govern the cancer hallmarks associated with bCSC, making them attractive targets for therapy. In this review, we present a current summary of the studies on the pivotal roles of lncRNAs and microRNAs in the regulation of genes associated to stemness of bCSC.

摘要

乳腺癌是一种侵袭性疾病,在全球女性中发病率很高。二十年前,有人提出了一个有争议的假说,即癌症起源于“肿瘤起始细胞”或“癌症干细胞样”(CSC)的亚群。如今,CSC被定义为肿瘤内一小部分具有自我更新特性的体细胞癌细胞,其由参与维持类似干性表型的基因异常表达所驱动。了解维持CSC亚群所涉及的潜在细胞和分子机制,对于乳腺癌的发生和持续发展至关重要。如今,该假说认为基因和表观遗传改变会产生乳腺癌干细胞(bCSC),它们负责自我更新、肿瘤生长、化疗耐药性、预后不良以及患者低生存率。然而,bCSC的突出地位以及调节和促进恶性表型的分子机制仍知之甚少。非编码RNA(ncRNA),如长链非编码RNA(lncRNA)和微小RNA(miRNA)作为癌基因或肿瘤抑制基因的作用,最近在大量乳腺癌研究中得到了强调。这些ncRNA对控制与bCSC相关癌症特征的不同信号通路产生正向或负向影响,使其成为有吸引力的治疗靶点。在本综述中,我们对lncRNA和miRNA在调节与bCSC干性相关基因中的关键作用的研究进行了当前总结。

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