Alsayed Reem Khaled M E, Khan Abdul Q, Ahmad Fareed, Ansari Abdul Wahid, Alam Majid Ali, Buddenkotte Jorg, Steinhoff Martin, Uddin Shahab, Ahmad Aamir
Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar.
Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar; Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar; Department of Dermatology and Venereology, Rumailah Hospital, Hamad Medical Corporation, Doha 3050, Qatar.
Semin Cancer Biol. 2022 Nov;86(Pt 2):697-708. doi: 10.1016/j.semcancer.2022.03.019. Epub 2022 Mar 26.
Signaling involving chemokine receptor CXCR4 and its ligand SDF-1/CXL12 has been investigated for many years for its possible role in cancer progression and pathogenesis. Evidence emerging from clinical studies in recent years has further established diagnostic as well as prognostic importance of CXCR4 signaling. CXCR4 and SDF-1 are routinely reported to be elevated in tumors, distant metastases, which correlates with poor survival of patients. These findings have kindled interest in the mechanisms that regulate CXCR4/SDF-1 expression. Of note, there is a particular interest in the epigenetic regulation of CXCR4 signaling that may be responsible for upregulated CXCR4 in primary as well as metastatic cancers. This review first lists the clinical evidence supporting CXCR4 signaling as putative cancer diagnostic and/or prognostic biomarker, followed by a discussion on reported epigenetic mechanisms that affect CXCR4 expression. These mechanisms include regulation by non-coding RNAs, such as, microRNAs, long non-coding RNAs and circular RNAs. Additionally, we also discuss the regulation of CXCR4 expression through methylation and acetylation. Better understanding and appreciation of epigenetic regulation of CXCR4 signaling can invariably lead to identification of novel therapeutic targets as well as therapies to regulate this oncogenic signaling.
涉及趋化因子受体CXCR4及其配体SDF-1/CXL12的信号传导因其在癌症进展和发病机制中的潜在作用已被研究多年。近年来临床研究得出的证据进一步确立了CXCR4信号传导在诊断和预后方面的重要性。常规报道称，CXCR4和SDF-1在肿瘤及远处转移灶中升高，这与患者的不良生存率相关。这些发现引发了人们对调节CXCR4/SDF-1表达机制的兴趣。值得注意的是，人们尤其关注CXCR4信号传导的表观遗传调控，其可能是原发性及转移性癌症中CXCR4上调的原因。本综述首先列出支持CXCR4信号传导作为假定癌症诊断和/或预后生物标志物的临床证据，随后讨论影响CXCR4表达的已报道表观遗传机制。这些机制包括非编码RNA的调控，如微小RNA、长链非编码RNA和环状RNA。此外，我们还讨论了通过甲基化和乙酰化对CXCR4表达的调控。更好地理解和认识CXCR4信号传导的表观遗传调控必然会导致鉴定新的治疗靶点以及调控这种致癌信号传导的疗法。
