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) |