Journal
CANCER AND METASTASIS REVIEWS
Volume 40, Issue 3, Pages 925-948Publisher
SPRINGER
DOI: 10.1007/s10555-021-09973-3
Keywords
miR-34a; miR-34b; c; Prognostic value; Functional roles; Downstream targets; Transcription factors; DNA methylation
Categories
Funding
- National Natural Science Foundation of China [81872892, 81773766, 82003811]
- Natural Science Foundation of Anhui Province [2008085QH403]
- Anhui Medical University [2019xkj002, XJ201917]
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miR-34 plays crucial roles in cancer, with its downstream targets involved in multiple signaling pathways and crucial biological processes. Among them, miR-34a is especially important and can effectively suppress tumor progression by combining with chemotherapy or radiotherapy.
MicroRNA-34 (miR-34) plays central roles in human diseases, especially cancers. Inactivation of miR-34 is detected in cancer cell lines and tumor tissues versus normal controls, implying its potential tumor-suppressive effect. Clinically, miR-34 has been identified as promising prognostic indicators for various cancers. In fact, members of the miR-34 family, especially miR-34a, have been convincingly proved to affect almost the whole cancer progression process. Here, a total of 512 (miR-34a, 10/21), 85 (miR-34b, 10/16), and 114 (miR-34c, 10/14) putative targets of miR-34a/b/c are predicted by at least ten miRNA databases, respectively. These targets are further analyzed in gene ontology (GO), KEGG pathway, and the Reactome pathway dataset. The results suggest their involvement in the regulation of signal transduction, macromolecule metabolism, and protein modification. Also, the targets are implicated in critical signaling pathways, such as MAPK, Notch, Wnt, PI3K/AKT, p53, and Ras, as well as apoptosis, cell cycle, and EMT-related pathways. Moreover, the upstream regulators of miR-34a, mainly including transcription factors (TFs), lncRNAs, and DNA methylation, will be summarized. Meanwhile, the potential TF upstream of miR-34a/b/c will be predicted by PROMO, JASPAR, Animal TFDB 3.0, and GeneCard databases. Notably, miR-34a is an attractive target for certain cancers. In fact, miR-34a-based systemic delivery combined with chemotherapy or radiotherapy can more effectively control tumor progression. Collectively, this review will provide a panorama for miR-34a in cancer research.
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