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Article

Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

1
Department of Oral Science, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
2
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
3
Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
4
Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Gianpaolo Papaccio
Int. J. Mol. Sci. 2021, 22(18), 9947; https://doi.org/10.3390/ijms22189947
Received: 16 August 2021 / Revised: 11 September 2021 / Accepted: 12 September 2021 / Published: 14 September 2021
(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)
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. View Full-Text
Keywords: microRNA; expression signature; miR-139-5p; miR-139-3p; HNSCC; tumor suppressor; passenger strand; GNA12; OLR1 microRNA; expression signature; miR-139-5p; miR-139-3p; HNSCC; tumor suppressor; passenger strand; GNA12; OLR1
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MDPI and ACS Style

Koma, A.; Asai, S.; Minemura, C.; Oshima, S.; Kinoshita, T.; Kikkawa, N.; Koshizuka, K.; Moriya, S.; Kasamatsu, A.; Hanazawa, T.; Uzawa, K.; Seki, N. Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma. Int. J. Mol. Sci. 2021, 22, 9947. https://doi.org/10.3390/ijms22189947

AMA Style

Koma A, Asai S, Minemura C, Oshima S, Kinoshita T, Kikkawa N, Koshizuka K, Moriya S, Kasamatsu A, Hanazawa T, Uzawa K, Seki N. Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2021; 22(18):9947. https://doi.org/10.3390/ijms22189947

Chicago/Turabian Style

Koma, Ayaka, Shunichi Asai, Chikashi Minemura, Sachi Oshima, Takashi Kinoshita, Naoko Kikkawa, Keiichi Koshizuka, Shogo Moriya, Atsushi Kasamatsu, Toyoyuki Hanazawa, Katsuhiro Uzawa, and Naohiko Seki. 2021. "Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma" International Journal of Molecular Sciences 22, no. 18: 9947. https://doi.org/10.3390/ijms22189947

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