缺氧是几乎所有实体肿瘤肿瘤微环境（TME）的常见特征，导致治疗失败。细胞外基质（ECM）的硬度变化，pH梯度和化学平衡对多种癌症特征的影响受到肿瘤内部氧气张力的严格调节，其主要介质是缺氧诱导因子（HIFs）。 HIFs，特别是HIF-1α，通过调节关键的癌症相关信号通路和细胞过程（包括MAPK / ERK，NF-κB，STAT3，PI3K / Akt，Wnt，p53和糖酵解）影响TME中的这些变化。有趣的是，研究揭示了缺氧调节的微小RNA（HRMs）参与了这些信号通路下游靶基因的表观遗传调控。通过文献搜索和分析，我们确定了48个HRMs，在缺氧条件下在各种癌症中对5个关键细胞过程的调节具有功能作用，包括增殖，代谢，存活，侵袭和迁移以及免疫调节。这些HRMs中，有17个直接与HIFs相关，包括miR-135b，miR-145，miR-155，miR-181a，miR-182，miR-210，miR-224，miR-301a和miR-675-5p作为oncomiRNAs以及miR-100-5p，miR-138，miR-138-5p，miR-153，miR-22，miR-338-3p，miR-519d-3p和miR-548an作为肿瘤抑制miRNAs。这些HRMs对于开发基于miRNA的靶向治疗晚期实体肿瘤具有潜在领先优势。未来发展组合HIF靶向和miRNA靶向治疗是可能的，需要全面综合分析HIFs-HRMs调节网络，并改进传递系统的配方以提高靶向肿瘤治疗（TCT）的治疗动力学。

Hypoxia is a common feature of the tumor microenvironment (TME) of nearly all solid tumors, leading to therapeutic failure. The changes in stiffness of the extracellular matrix (ECM), pH gradients, and chemical balance that contribute to multiple cancer hallmarks are closely regulated by intratumoral oxygen tension via its primary mediators, hypoxia-inducible factors (HIFs). HIFs, especially HIF-1α, influence these changes in the TME by regulating vital cancer-associated signaling pathways and cellular processes including MAPK/ERK, NF-κB, STAT3, PI3K/Akt, Wnt, p53, and glycolysis. Interestingly, research has revealed the involvement of epigenetic regulation by hypoxia-regulated microRNAs (HRMs) of downstream target genes involved in these signaling. Through literature search and analysis, we identified 48 HRMs that have a functional role in the regulation of 5 key cellular processes: proliferation, metabolism, survival, invasion and migration, and immunoregulation in various cancers in hypoxic condition. Among these HRMs, 17 were identified to be directly associated with HIFs which include miR-135b, miR-145, miR-155, miR-181a, miR-182, miR-210, miR-224, miR-301a, and miR-675-5p as oncomiRNAs, and miR-100-5p, miR-138, miR-138-5p, miR-153, miR-22, miR-338-3p, miR-519d-3p, and miR-548an as tumor suppressor miRNAs. These HRMs serve as a potential lead in the development of miRNA-based targeted therapy for advanced solid tumors. Future development of combined HIF-targeted and miRNA-targeted therapy is possible, which requires comprehensive profiling of HIFs-HRMs regulatory network, and improved formula of the delivery vehicles to enhance the therapeutic kinetics of the targeted cancer therapy (TCT) moving forward.