Departments of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Departments of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Cells. 2020 Mar 20;9(3):763. doi: 10.3390/cells9030763.
Treatment decisions for breast cancer are based on staging and hormone receptor expression and include chemotherapies and endocrine therapy. While effective in many cases, some breast cancers are resistant to therapy, metastasize and recur, leading to eventual death. Higher percentages of tumor-initiating cancer stem cells (CSCs) may contribute to the increased aggressiveness, chemoresistance, and worse outcomes among breast cancer. This may be particularly true in triple-negative breast cancers (TNBCs) which have higher percentages of CSCs and are associated with worse outcomes. In recent years, increasing numbers of long non-coding RNAs (lncRNAs) have been identified as playing an important role in breast cancer progression and some of these have been specifically associated within the CSC populations of breast cancers. LncRNAs are non-protein-coding transcripts greater than 200 nucleotides which can have critical functions in gene expression regulation. The preclinical evidence regarding lncRNA antagonists for the treatment of cancer is promising and therefore, presents a potential novel approach for treating breast cancer and targeting therapy-resistant CSCs within these tumors. Herein, we summarize the lncRNAs that have been identified as functionally relevant in breast CSCs. Furthermore, our review of the literature and analysis of patient datasets has revealed that many of these breast CSC-associated lncRNAs are also enriched in TNBC. Together, this suggests that these lncRNAs may be playing a particularly important role in TNBC. Thus, certain breast cancer-promoting/CSC-associated lncRNAs could be targeted in the treatment of TNBCs and the CSCs within these tumors should be susceptible to anti-lncRNA therapy.
乳腺癌的治疗决策基于分期和激素受体表达，包括化疗和内分泌治疗。虽然在许多情况下有效，但有些乳腺癌对治疗有抗药性，转移和复发，最终导致死亡。肿瘤起始癌症干细胞 (CSC) 的比例较高可能导致乳腺癌的侵袭性增加、化疗耐药性和预后较差。这在三阴性乳腺癌 (TNBC) 中可能更为明显，因为 TNBC 中 CSC 的比例较高，且与预后较差相关。近年来，越来越多的长链非编码 RNA (lncRNA) 被确定在乳腺癌的进展中发挥重要作用，其中一些与乳腺癌 CSC 群体特异性相关。lncRNA 是大于 200 个核苷酸的非蛋白编码转录物，在基因表达调控中具有关键功能。lncRNA 拮抗剂治疗癌症的临床前证据很有前景，因此为治疗乳腺癌和针对这些肿瘤中的耐药性 CSC 提供了一种潜在的新方法。本文总结了在乳腺癌 CSC 中被确定为具有功能相关性的 lncRNA。此外，我们对文献的综述和对患者数据集的分析表明，这些与乳腺癌 CSC 相关的 lncRNA 中的许多也在 TNBC 中富集。综上所述，这表明这些 lncRNA 可能在 TNBC 中发挥特别重要的作用。因此，某些促进乳腺癌/CSC 相关的 lncRNA 可作为 TNBC 的治疗靶点，并且这些肿瘤中的 CSC 应该对反 lncRNA 治疗敏感。
