Department of Biochemistry & Molecular Biology, Rajshahi University, Rajshahi, Bangladesh.
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Cancer Med. 2023 Oct;12(20):20365-20379. doi: 10.1002/cam4.6600. Epub 2023 Oct 5.
Long noncoding RNAs (lncRNAs) play crucial roles in regulating various hallmarks in cancers. Triple-negative (Estrogen receptor, ER; Human epidermal growth factor receptor 2, HER2; Progesterone receptor, PR) breast cancer (TNBC) is the most aggressive form of breast cancers with a poor prognosis and no available molecular targeted therapy.
We reviewed the current literature on the roles of lncRNAs in the pathogenesis, therapy resistance, and prognosis of patients with TBNC.
LncRNAs are associated with TNBC pathogenesis, therapy resistance, and prognosis. For example, lncRNAs such as small nucleolar RNA host gene 12 (SNHG12), highly upregulated in liver cancer (HULC) HOX transcript antisense intergenic RNA (HOTAIR), lincRNA-regulator of reprogramming (LincRNA-ROR), etc., are aberrantly expressed in TNBC and are involved in the pathogenesis of the disease. LncRNAs act as a decoy, scaffold, or sponge to regulate the expression of genes, miRNAs, and transcription factors associated with pathogenesis and progression of TNBC. Moreover, lncRNAs such as ferritin heavy chain 1 pseudogene 3 (FTH1P3), BMP/OP-responsive gene (BORG) contributes to the therapy resistance property of TNBC through activating ABCB1 (ATP-binding cassette subfamily B member 1) drug efflux pumps by increasing DNA repair capacity or by inducing signaling pathway involved in therapeutic resistance.
In this review, we outline the functions of various lncRNAs along with their molecular mechanisms involved in the pathogenesis, therapeutic resistance of TBNC. Also, the prognostic implications of lncRNAs in patients with TNBC is illustrated. Moreover, potential strategies targeting lncRNAs against highly aggressive TNBC is discussed in this review.
长链非编码 RNA(lncRNAs)在调节癌症的各种特征方面发挥着关键作用。三阴性(雌激素受体,ER;人表皮生长因子受体 2,HER2;孕激素受体,PR)乳腺癌(TNBC)是乳腺癌中最具侵袭性的一种,预后较差,目前尚无可用的分子靶向治疗方法。
我们回顾了目前关于 lncRNAs 在 TNBC 患者发病机制、治疗耐药性和预后中的作用的文献。
lncRNAs 与 TNBC 的发病机制、治疗耐药性和预后有关。例如,lncRNAs 如小核仁 RNA 宿主基因 12(SNHG12)、肝癌高表达的 HOX 转录反义基因间 RNA(HOTAIR)、lncRNA 调控重编程(LincRNA-ROR)等,在 TNBC 中异常表达,并参与疾病的发病机制。lncRNAs 作为诱饵、支架或海绵,调节与 TNBC 发病机制和进展相关的基因、miRNA 和转录因子的表达。此外,铁蛋白重链 1 假基因 3(FTH1P3)、BMP/OP 反应基因(BORG)等 lncRNAs 通过增加 DNA 修复能力或诱导与治疗耐药性相关的信号通路,增加 ABCB1(ATP 结合盒亚家族 B 成员 1)药物外排泵的活性,从而有助于 TNBC 的治疗耐药性。
在本综述中,我们概述了各种 lncRNAs 的功能及其在 TNBC 的发病机制、治疗耐药性中的分子机制。还说明了 lncRNAs 在 TNBC 患者中的预后意义。此外,本文还讨论了针对高度侵袭性 TNBC 靶向 lncRNAs 的潜在策略。