ncRNA 和外泌体在子宫内膜癌发生和进展中的作用。
The role of ncRNAs and exosomes in the development and progression of endometrial cancer.
发表日期:2024
作者:
Julia Niebora, Sławomir Woźniak, Dominika Domagała, Krzysztof Data, Maryam Farzaneh, Mojtaba Zehtabi, Mahrokh Abouali Gale Dari, Fatemeh Khojasteh Pour, Artur Bryja, Magdalena Kulus, Paul Mozdziak, Piotr Dzięgiel, Bartosz Kempisty
来源:
Epigenetics & Chromatin
摘要:
子宫内膜癌(EC)是最常见的妇科癌症之一。近年来,研究重点关注肿瘤的遗传特征,以详细说明其预后并制定治疗方案。就 EC 而言,基因突变已被证明是其形成的基础。了解与雌激素等诱导突变相关的 EC 形成机制非常重要。非编码 RNA (ncRNA) 由蛋白质编码能力极低的核苷酸转录物组成,已被证明非常重要。它们在许多恶性肿瘤中的表达模式可以抑制肿瘤的形成和进展。它们还在表观遗传、转录和转录后水平上调节蛋白质编码。 MicroRNA (miRNA) 的多种类型与正常子宫内膜及其肿瘤相关,在基因表达中也发挥着特别重要的作用。 miRNA 和长链非编码 RNA (lncRNA) 影响 EC 组织中的许多通路,并在癌症发生、侵袭和转移以及通过抑制癌症干细胞凋亡和进展等机制对抗癌药物产生耐药性中发挥重要作用。还值得注意的是,miRNA 具有高度精确性、敏感性和稳健性,使其成为诊断妇科癌症及其进展的潜在标记。不幸的是,随着 EC 发病率的增加,治疗变得具有挑战性并且仅限于侵入性工具。使用 microRNA 作为 EC 诊断和治疗用途的潜在候选者的前景似乎很有希望。外泌体是多种细胞(包括癌细胞)释放的细胞外囊泡。它们含有蛋白质、DNA 和各种类型的 RNA,例如 miRNA。外泌体的非编码 RNA 成分差异很大,具体取决于肿瘤组织及其来源细胞的生理学。外泌体含有DNA和RNA,具有细胞间通讯功能。外泌体 miRNA 介导 EC 细胞、肿瘤相关成纤维细胞 (CAF) 和肿瘤相关巨噬细胞 (TAM) 之间的通讯,并在肿瘤细胞增殖和肿瘤微环境形成中发挥关键作用。肿瘤外泌体携带的癌基因诱导靶细胞恶性转化。在外泌体的合成过程中,遗传和蛋白质组数据等各种因素都会上调。因此,通过分析外泌体中包含的生物标志物,它们被认为是子宫内膜癌诊断和预后的一个有趣的治疗靶点。来自 EC 患者血浆的外泌体中 miRNA,尤其是 miR-15a-5p 的表达升高。这可能表明该生物标志物在 EC 诊断中的重要用途。近年来,研究人员对子宫内膜癌的预后标志物这一主题产生了兴趣,因为已识别的标志物仍然太少,无法支持子宫内膜癌的有限治疗。进一步研究 ncRNA 和外泌体对 EC 的影响可能会实现癌症治疗的突破。版权所有 © 2024 Niebora、Woźniak、Domagała、Data、Farzaneh、Zehtabi、Dari、Pour、Bryja、Kulus、Mozdziak、Dzięgiel 和 Kempisty。
Endometrial cancer (EC) is one of the most common gynecologic cancers. In recent years, research has focused on the genetic characteristics of the tumors to detail their prognosis and tailor therapy. In the case of EC, genetic mutations have been shown to underlie their formation. It is very important to know the mechanisms of EC formation related to mutations induced by estrogen, among other things. Noncoding RNAs (ncRNAs), composed of nucleotide transcripts with very low protein-coding capacity, are proving to be important. Their expression patterns in many malignancies can inhibit tumor formation and progression. They also regulate protein coding at the epigenetic, transcriptional, and posttranscriptional levels. MicroRNAs (miRNAs), several varieties of which are associated with normal endometrium as well as its tumor, also play a particularly important role in gene expression. MiRNAs and long noncoding RNAs (lncRNAs) affect many pathways in EC tissues and play important roles in cancer development, invasion, and metastasis, as well as resistance to anticancer drugs through mechanisms such as suppression of apoptosis and progression of cancer stem cells. It is also worth noting that miRNAs are highly precise, sensitive, and robust, making them potential markers for diagnosing gynecologic cancers and their progression. Unfortunately, as the incidence of EC increases, treatment becomes challenging and is limited to invasive tools. The prospect of using microRNAs as potential candidates for diagnostic and therapeutic use in EC seems promising. Exosomes are extracellular vesicles that are released from many types of cells, including cancer cells. They contain proteins, DNA, and various types of RNA, such as miRNAs. The noncoding RNA components of exosomes vary widely, depending on the physiology of the tumor tissue and the cells from which they originate. Exosomes contain both DNA and RNA and have communication functions between cells. Exosomal miRNAs mediate communication between EC cells, tumor-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs) and play a key role in tumor cell proliferation and tumor microenvironment formation. Oncogenes carried by tumor exosomes induce malignant transformation of target cells. During the synthesis of exosomes, various factors, such as genetic and proteomic data are upregulated. Thus, they are considered an interesting therapeutic target for the diagnosis and prognosis of endometrial cancer by analyzing biomarkers contained in exosomes. Expression of miRNAs, particularly miR-15a-5p, was elevated in exosomes derived from the plasma of EC patients. This may suggest the important utility of this biomarker in the diagnosis of EC. In recent years, researchers have become interested in the topic of prognostic markers for EC, as there are still too few identified markers to support the limited treatment of endometrial cancer. Further research into the effects of ncRNAs and exosomes on EC may allow for cancer treatment breakthroughs.Copyright © 2024 Niebora, Woźniak, Domagała, Data, Farzaneh, Zehtabi, Dari, Pour, Bryja, Kulus, Mozdziak, Dzięgiel and Kempisty.