Targeting Transient Receptor Potential Channels by MicroRNAs Drives Tumor Development and Progression
Targeting Transient Receptor Potential Channels by MicroRNAs Drives Tumor Development and Progression
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DOI：
10.1007/978-3-030-12457-1_24
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发表时间：
2020-01-01
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影响因子：
--
通讯作者：
Amantini, Consuelo
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文献类型：
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作者：
Santoni, Giorgio;Morelli, Maria Beatrice;Amantini, Consuelo
瞬时受体电位（TRP）阳离子通道超家族在多种细胞过程中发挥重要作用，如多模态细胞感受、粘附、极性、增殖、分化和凋亡等。TRP通道的表达受到严格的调控，其失调可刺激肿瘤的发生和发展，在人类肿瘤中，特异性的miRNAs在不同的组织中表达，由特异性miRNAs介导的基因表达调控的改变与肿瘤的发生有关。已经报道了几种miRNA/TRP通道对在肿瘤生物学中起重要作用。因此，TRPM 1基因通过TRPM 1和microRNA-211转录物调节黑素细胞/黑素瘤行为。miR-211和TRPM 1蛋白均通过小眼症相关转录因子（MIFT）调节，并且在黑色素瘤进展期间miR-211的表达减少。黑素细胞表型和黑色素瘤行为严格依赖于双重TRPM 1活性，TRPM 1蛋白的缺失促进黑色素瘤侵袭性，而miR-211表达支持肿瘤抑制因子。TRPM 3在具有von Hippel-Lindau（VHL）损失的人透明细胞肾细胞癌（ccRCC）的发展和进展中起主要作用。TRPM 3是miR-204的直接靶点，在具有失活或缺失的VHL的ccRCC中增强。VHL的缺失抑制miR-204表达，导致致癌性自噬增加。因此，对不同肿瘤中特异性TRP通道/miRNA分子通路的理解可以为癌症的靶向治疗提供临床依据。
Transient receptor potential (TRP) cation channel superfamily plays important roles in a variety of cellular processes such polymodal cellular sensing, adhesion, polarity, proliferation, differentiation and apoptosis. The expression of TRP channels is strictly regulated and their de-regulation can stimulate cancer development and progression.In human cancers, specific miRNAs are expressed in different tissues, and changes in the regulation of gene expression mediated by specific miRNAs have been associated with carcinogenesis. Several miRNAs/TRP channel pairs have been reported to play an important role in tumor biology. Thus, the TRPM1 gene regulates melanocyte/melanoma behaviour via TRPM1 and microRNA-211 transcripts. Both miR-211 and TRPM1 proteins are regulated through microphthalmia-associated transcription factor (MIFT) and the expression of miR-211 is decreased during melanoma progression. Melanocyte phenotype and melanoma behaviour strictly depend on dual TRPM1 activity, with loss of TRPM1 protein promoting melanoma aggressiveness and miR-211 expression supporting tumour suppressor. TRPM3 plays a major role in the development and progression of human clear cell renal cell carcinoma (ccRCC) with von Hippel-Lindau (VHL) loss. TRPM3, a direct target of miR-204, is enhanced in ccRCC with inactivated or deleted VHL. Loss of VHL inhibits miR-204 expression that lead to increased oncogenic autophagy. Therefore, the understanding of specific TRP channels/miRNAs molecular pathways in distinct tumors could provide a clinical rationale for target therapy in cancer.