Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 233, Issue 9, Pages 6660-6668Publisher
WILEY
DOI: 10.1002/jcp.26316
Keywords
colorectal cancer; microRNA; NF-B; TLR4
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Funding
- National Natural Science Foundation of China [81601408]
- Shandong Natural Science Foundation for Young Scholars [ZR2016HQ12]
- Shandong Medical and Health Science and Technology Development Program [2015WS0052, 2015WS0085, 2016WS0681, 2016WS0686]
- Weifang Science and Technology Development Program [2016YX016, 2017YX019]
- Weifang Medical University [02173401]
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Many studies have implicated that microRNAs (miRNAs), as non-coding RNAs, play important roles in the development and progression of colorectal cancer (CRC). However, little is known about the role of a newly identified miRNA, miR-6869-5p, in CRC. We aim to investigate the modifying effects and underlying mechanisms of miR-6869-5 in colorectal carcinogenesis and progression. Significantly reduced levels of miR-6869-5p were observed in both serum exosomes tumor tissue samples from patients with CRC. The prediction of targets of miR-6869-5p in databases of targetscan, microRNA. ORG and miRDBA revealed that toll-like receptor 4 (TLR4) is a potential target for this miRNA. MiR-6869-5p could inhibit cell proliferation and the production of inflammatory cytokines (TNF- and IL-6) in CRC cells via directly targeting TLR4. The protective effect of miR-6869-5p from colorectal carcinogenesis was dependent on TLR4/NF-B signaling pathway. In addition, the 3-year survival was poor among CRC patients with decreased levels of miR-6869-5p in serum exosomes. Thus, miR-6869-5p may serve as a tumor suppressor in CRC, and serum exosomal miR-6869-5p is a promising circulating biomarker for the prediction of CRC prognosis.
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