Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.
Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang, 110122, People's Republic of China.
Mol Cancer. 2022 May 17;21(1):115. doi: 10.1186/s12943-022-01591-z.
Cancer is a type of malignant affliction threatening human health worldwide; however, the molecular mechanism of cancer pathogenesis remains to be elusive. The oncogenic hedgehog (Hh) pathway is a highly evolutionarily conserved signaling pathway in which the hedgehog-Patched complex is internalized to cellular lysosomes for degradation, resulting in the release of Smoothened inhibition and producing downstream intracellular signals. Noncoding RNAs (ncRNAs) with diversified regulatory functions have the potency of controlling cellular processes. Compelling evidence reveals that Hh pathway, ncRNAs, or their crosstalk play complicated roles in the initiation, metastasis, apoptosis and drug resistance of cancer, allowing ncRNAs related to the Hh pathway to serve as clinical biomarkers for targeted cancer therapy. In this review, we attempt to depict the multiple patterns of ncRNAs in the progression of malignant tumors via interactions with the Hh crucial elements in order to better understand the complex regulatory mechanism, and focus on Hh associated ncRNA therapeutics aimed at boosting their application in the clinical setting.
癌症是一种威胁全球人类健康的恶性疾病;然而,癌症发病机制的分子机制仍然难以捉摸。致癌刺猬(Hh)途径是一种高度进化保守的信号通路,其中刺猬-Patched 复合物被内化到细胞溶酶体中进行降解,导致 Smoothened 抑制物的释放,并产生下游细胞内信号。具有多样化调控功能的非编码 RNA(ncRNA)具有调控细胞过程的能力。令人信服的证据表明,Hh 途径、ncRNA 或它们的串扰在癌症的发生、转移、凋亡和耐药性中发挥着复杂的作用,使得与 Hh 途径相关的 ncRNA 可以作为癌症靶向治疗的临床生物标志物。在这篇综述中,我们试图通过与 Hh 关键元素的相互作用来描述 ncRNA 在恶性肿瘤进展中的多种模式,以便更好地理解复杂的调控机制,并专注于 Hh 相关的 ncRNA 治疗,旨在促进它们在临床环境中的应用。