RRC ID 69745
著者 Koma A, Asai S, Minemura C, Oshima S, Kinoshita T, Kikkawa N, Koshizuka K, Moriya S, Kasamatsu A, Hanazawa T, Uzawa K, Seki N.
タイトル Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma.
ジャーナル Int J Mol Sci
Abstract We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.
巻・号 22(18)
公開日 2021-9-14
DOI 10.3390/ijms22189947
PII ijms22189947
PMID 34576110
PMC PMC8469660
MeSH Base Sequence Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Gene Expression Profiling Gene Expression Regulation, Neoplastic* Head and Neck Neoplasms / genetics* Head and Neck Neoplasms / pathology Humans MicroRNAs / genetics* MicroRNAs / metabolism Neoplasm Invasiveness Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Oncogenes* RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction / genetics Squamous Cell Carcinoma of Head and Neck / genetics* Squamous Cell Carcinoma of Head and Neck / pathology
IF 4.556
リソース情報
ヒト・動物細胞 Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Sa38RCB0980) SAS(RCB1974) HO-1-u-1(RCB2102)