H Al-Zuaini Hashim, Rafiq Zahid Kashif, Xiao Xiangyan, Raza Umar, Huang Qiyuan, Zeng Tao
Pharmacy Department, Al-kut University College, Kut, Iraq.
Department of Medical Laboratory, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Front Oncol. 2023 Jul 31;13:1207253. doi: 10.3389/fonc.2023.1207253. eCollection 2023.
Low oxygen tension, or hypoxia is the driving force behind tumor aggressiveness, leading to therapy resistance, metastasis, and stemness in solid cancers including breast cancer, which now stands as the leading cause of cancer-related mortality in women. With the great advancements in exploring the regulatory roles of the non-coding genome in recent years, the wide spectrum of hypoxia-responsive genome is not limited to just protein-coding genes but also includes multiple types of non-coding RNAs, such as micro RNAs, long non-coding RNAs, and circular RNAs. Over the years, these hypoxia-responsive non-coding molecules have been greatly implicated in breast cancer. Hypoxia drives the expression of these non-coding RNAs as upstream modulators and downstream effectors of hypoxia inducible factor signaling in the favor of breast cancer through a myriad of molecular mechanisms. These non-coding RNAs then contribute in orchestrating aggressive hypoxic tumor environment and regulate cancer associated cellular processes such as proliferation, evasion of apoptotic death, extracellular matrix remodeling, angiogenesis, migration, invasion, epithelial-to-mesenchymal transition, metastasis, therapy resistance, stemness, and evasion of the immune system in breast cancer. In addition, the interplay between hypoxia-driven non-coding RNAs as well as feedback and feedforward loops between these ncRNAs and HIFs further contribute to breast cancer progression. Although the current clinical implications of hypoxia-driven non-coding RNAs are limited to prognostics and diagnostics in breast cancer, extensive explorations have established some of these hypoxia-driven non-coding RNAs as promising targets to treat aggressive breast cancers, and future scientific endeavors hold great promise in targeting hypoxia-driven ncRNAs at clinics to treat breast cancer and limit global cancer burden.
低氧张力，即缺氧，是肿瘤侵袭性的驱动力，导致实体癌（包括乳腺癌，目前是女性癌症相关死亡的主要原因）产生治疗抗性、转移和干性。近年来，随着在探索非编码基因组调控作用方面取得的巨大进展，缺氧反应性基因组的范围不仅限于蛋白质编码基因，还包括多种类型的非编码RNA，如微小RNA、长链非编码RNA和环状RNA。多年来，这些缺氧反应性非编码分子与乳腺癌密切相关。缺氧通过多种分子机制驱动这些非编码RNA的表达，使其成为缺氧诱导因子信号传导的上游调节因子和下游效应器，从而促进乳腺癌的发展。这些非编码RNA随后有助于构建侵袭性缺氧肿瘤环境，并调节乳腺癌中与癌症相关的细胞过程，如增殖、逃避凋亡死亡、细胞外基质重塑、血管生成、迁移、侵袭、上皮-间质转化、转移、治疗抗性、干性以及逃避免疫系统。此外，缺氧驱动的非编码RNA之间的相互作用以及这些非编码RNA与缺氧诱导因子之间的反馈和前馈环进一步促进了乳腺癌的进展。尽管目前缺氧驱动的非编码RNA在临床上的意义仅限于乳腺癌的预后和诊断，但广泛的探索已将其中一些缺氧驱动的非编码RNA确立为治疗侵袭性乳腺癌的有前景的靶点，未来的科学研究有望在临床上针对缺氧驱动的非编码RNA来治疗乳腺癌并减轻全球癌症负担。
