Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma
Abstract
:1. Introduction
2. Results
2.1. Identification of the miRNA Expression Signature of HNSCC by RNA Sequencing
2.2. Expression Levels and Clinical Significance of miR-31-5p and miR-31-3p in HNSCC
2.3. Effects of Inhibition of miR-31-5p and miR-31-3p Expression on the Proliferation, Migration, and Invasion of HNSCC Cells
2.4. Screening of miR-31-5p and miR-31-3p Targets in HNSCC Cells
2.5. Clinical Significance of miR-31-5p and miR-31-3p Targets in HNSCC Cells
2.6. Direct Regulation of CGNL1 by miR-31-3p in HNSCC Cells
3. Discussion
4. Materials and Methods
4.1. Clinical HNSCC and Normal Epithelial Tissue Specimens and HNSCC Cell Lines
4.2. Determination of the miRNA Expression Signature in HNSCC by RNA Sequencing
4.3. RNA Extraction and Quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR)
4.4. Transfection of Mirnas Precursors and Inhibitors into HNSCC Cells
4.5. Functional Assays (Cell Proliferation, Migration, and Invasion) in HNSCC Cells
4.6. Analysis of the Clinical Significance of HNSCC Patients Using TCGA-HNSC Data
4.7. Western Blotting
4.8. Plasmid Construction and Dual-Luciferase Reporter Assays
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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A | ||||
---|---|---|---|---|
Entrez Gene ID | Gene Symbol | Gene Name | Fold Change (log2 < −2.0) | Total Sites |
5563 | PRKAA2 | protein kinase, AMP-activated, alpha 2 catalytic subunit | −4.56 | 1 |
83699 | SH3BGRL2 | SH3 domain binding glutamate-rich protein like 2 | −4.45 | 1 |
6517 | SLC2A4 | solute carrier family 2 (facilitated glucose transporter), member 4 | −4.29 | 1 |
2252 | FGF7 | fibroblast growth factor 7 | −3.81 | 1 |
55607 | PPP1R9A | protein phosphatase 1, regulatory subunit 9A | −3.73 | 1 |
5549 | PRELP | proline/arginine-rich end leucine-rich repeat protein | −3.66 | 2 |
5083 | PAX9 | paired box 9 | −3.62 | 1 |
26084 | ARHGEF26 | Rho guanine nucleotide exchange factor (GEF) 26 | −3.58 | 1 |
252995 | FNDC5 | fibronectin type III domain containing 5 | −3.50 | 1 |
51209 | RAB9B | RAB9B, member RAS oncogene family | −3.23 | 1 |
2899 | GRIK3 | glutamate receptor, ionotropic, kainate 3 | −2.88 | 1 |
401474 | SAMD12 | sterile alpha motif domain containing 12 | −2.84 | 1 |
60529 | ALX4 | ALX homeobox 4 | −2.63 | 1 |
64399 | HHIP | hedgehog interacting protein | −2.53 | 1 |
146433 | IL34 | interleukin 34 | −2.45 | 1 |
84144 | SYDE2 | synapse defective 1, Rho GTPase, homolog 2 (C. elegans) | −2.44 | 2 |
619279 | ZNF704 | zinc finger protein 704 | −2.40 | 1 |
783 | CACNB2 | calcium channel, voltage-dependent, beta 2 subunit | −2.34 | 1 |
5493 | PPL | periplakin | −2.27 | 1 |
3670 | ISL1 | ISL LIM homeobox 1 | −2.24 | 2 |
389208 | TMPRSS11F | transmembrane protease, serine 11F | −2.17 | 1 |
168667 | BMPER | BMP binding endothelial regulator | −2.16 | 1 |
1983 | EIF5 | eukaryotic translation initiation factor 5 | −2.14 | 1 |
5100 | PCDH8 | protocadherin 8 | −2.06 | 2 |
B | ||||
Entrez Gene ID | Gene Symbol | Gene Name | Fold Change (log2 < −2.0) | Total Sites |
420 | ART4 | ADP-ribosyltransferase 4 (Dombrock blood group) | −6.92 | 1 |
5075 | PAX1 | paired box 1 | −6.47 | 1 |
1805 | DPT | dermatopontin | −5.69 | 1 |
10218 | ANGPTL7 | angiopoietin-like 7 | −5.09 | 1 |
2315 | MLANA | melan-A | −4.81 | 1 |
55286 | C4orf19 | chromosome 4 open reading frame 19 | −4.76 | 1 |
8839 | WISP2 | WNT1 inducible signaling pathway protein 2 | −4.72 | 1 |
440854 | CAPN14 | calpain 14 | −4.70 | 1 |
6422 | SFRP1 | secreted frizzled-related protein 1 | −4.70 | 1 |
114905 | C1QTNF7 | C1q and tumor necrosis factor related protein 7 | −4.66 | 1 |
9068 | ANGPTL1 | angiopoietin-like 1 | −4.56 | 1 |
5563 | PRKAA2 | protein kinase, AMP-activated, alpha 2 catalytic subunit | −4.56 | 2 |
5104 | SERPINA5 | serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 5 | −4.45 | 1 |
148213 | ZNF681 | zinc finger protein 681 | −4.27 | 1 |
127435 | PODN | podocan | −4.20 | 1 |
53405 | CLIC5 | chloride intracellular channel 5 | −4.16 | 1 |
85477 | SCIN | scinderin | −4.09 | 1 |
255798 | SMCO1/C3orf43 | single-pass membrane protein with coiled-coil domains 1 | −4.01 | 1 |
53353 | LRP1B | low density lipoprotein receptor-related protein 1B | −4.00 | 1 |
23242 | COBL | cordon-bleu WH2 repeat protein | −3.89 | 1 |
5570 | PKIB | protein kinase (cAMP-dependent, catalytic) inhibitor beta | −3.84 | 1 |
440730 | TRIM67 | tripartite motif containing 67 | −3.83 | 1 |
2252 | FGF7 | fibroblast growth factor 7 | −3.81 | 1 |
84525 | HOPX | HOP homeobox | −3.81 | 1 |
389432 | SAMD5 | sterile alpha motif domain containing 5 | −3.79 | 1 |
8736 | MYOM1 | myomesin 1 | −3.68 | 1 |
5549 | PRELP | proline/arginine-rich end leucine-rich repeat protein | −3.66 | 2 |
137735 | ABRA | actin-binding Rho activating protein | −3.58 | 1 |
785 | CACNB4 | calcium channel, voltage-dependent, beta 4 subunit | −3.57 | 3 |
79442 | LRRC2 | leucine rich repeat containing 2 | −3.55 | 2 |
339512 | C1orf110 | chromosome 1 open reading frame 110 | −3.50 | 1 |
10894 | LYVE1 | lymphatic vessel endothelial hyaluronan receptor 1 | −3.43 | 1 |
3768 | KCNJ12 | potassium channel, inwardly rectifying subfamily J, member 12 | −3.36 | 1 |
171024 | SYNPO2 | synaptopodin 2 | −3.35 | 1 |
114786 | XKR4 | XK, Kell blood group complex subunit-related family, member 4 | −3.33 | 1 |
84952 | CGNL1 | cingulin-like 1 | −3.30 | 2 |
55335 | NIPSNAP3B | nipsnap homolog 3B (C. elegans) | −3.27 | 1 |
3479 | IGF1 | insulin-like growth factor 1 (somatomedin C) | −3.26 | 2 |
2690 | GHR | growth hormone receptor | −3.20 | 1 |
8522 | GAS7 | growth arrest-specific 7 | −3.18 | 1 |
2066 | ERBB4 | erb-b2 receptor tyrosine kinase 4 | −3.14 | 2 |
202333 | CMYA5 | cardiomyopathy associated 5 | −3.13 | 1 |
22865 | SLITRK3 | SLIT and NTRK-like family, member 3 | −3.13 | 1 |
51666 | ASB4 | ankyrin repeat and SOCS box containing 4 | −3.08 | 1 |
22871 | NLGN1 | neuroligin 1 | −3.08 | 1 |
4958 | OMD | osteomodulin | −3.08 | 1 |
5178 | PEG3 | paternally expressed 3 | −3.06 | 1 |
29119 | CTNNA3 | catenin (cadherin-associated protein), alpha 3 | −3.04 | 2 |
8529 | CYP4F2 | cytochrome P450, family 4, subfamily F, polypeptide 2 | −3.01 | 1 |
343450 | KCNT2 | potassium channel, sodium activated subfamily T, member 2 | −3.00 | 1 |
5087 | PBX1 | pre-B-cell leukemia homeobox 1 | −2.98 | 1 |
387758 | FIBIN | fin bud initiation factor homolog (zebrafish) | −2.96 | 1 |
57689 | LRRC4C | leucine rich repeat containing 4C | −2.96 | 1 |
79071 | ELOVL6 | ELOVL fatty acid elongase 6 | −2.95 | 1 |
6542 | SLC7A2 | solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 | −2.94 | 1 |
6450 | SH3BGR | SH3 domain binding glutamate-rich protein | −2.93 | 1 |
7276 | TTR | transthyretin | −2.92 | 2 |
23732 | FRRS1L/C9orf4 | ferric-chelate reductase 1-like | −2.89 | 1 |
220963 | SLC16A9 | solute carrier family 16, member 9 | −2.88 | 1 |
55 | ACPP | acid phosphatase, prostate | −2.84 | 1 |
401474 | SAMD12 | sterile alpha motif domain containing 12 | −2.84 | 1 |
8153 | RND2 | Rho family GTPase 2 | −2.83 | 1 |
7135 | TNNI1 | troponin I type 1 (skeletal, slow) | −2.82 | 1 |
340596 | LHFPL1 | lipoma HMGIC fusion partner-like 1 | −2.77 | 1 |
26974 | ZNF285 | zinc finger protein 285 | −2.74 | 1 |
2053 | EPHX2 | epoxide hydrolase 2, cytoplasmic | −2.73 | 1 |
386618 | KCTD4 | potassium channel tetramerization domain containing 4 | −2.73 | 1 |
1183 | CLCN4 | chloride channel, voltage-sensitive 4 | −2.69 | 1 |
291 | SLC25A4 | solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4 | −2.68 | 1 |
4023 | LPL | lipoprotein lipase | −2.65 | 1 |
32 | ACACB | acetyl-CoA carboxylase beta | −2.64 | 1 |
55244 | SLC47A1 | solute carrier family 47 (multidrug and toxin extrusion), member 1 | −2.64 | 1 |
84620 | ST6GAL2 | ST6 beta-galactosamide alpha-2,6-sialyltranferase 2 | −2.62 | 1 |
26032 | SUSD5 | sushi domain containing 5 | −2.61 | 1 |
6857 | SYT1 | synaptotagmin I | −2.61 | 2 |
6391 | SDHC | succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa | −2.60 | 1 |
5506 | PPP1R3A | protein phosphatase 1, regulatory subunit 3A | −2.58 | 2 |
367 | AR | androgen receptor | −2.57 | 2 |
64399 | HHIP | hedgehog interacting protein | −2.53 | 1 |
56898 | BDH2 | 3-hydroxybutyrate dehydrogenase, type 2 | −2.52 | 2 |
9077 | DIRAS3 | DIRAS family, GTP-binding RAS-like 3 | −2.52 | 1 |
154661 | RUNDC3B | RUN domain containing 3B | −2.52 | 1 |
8796 | SCEL | sciellin | −2.52 | 1 |
50937 | CDON | cell adhesion associated, oncogene regulated | −2.49 | 1 |
6660 | SOX5 | SRY (sex determining region Y)-box 5 | −2.48 | 1 |
56172 | ANKH | ANKH inorganic pyrophosphate transport regulator | −2.46 | 1 |
6092 | ROBO2 | roundabout, axon guidance receptor, homolog 2 (Drosophila) | −2.46 | 1 |
158326 | FREM1 | FRAS1 related extracellular matrix 1 | −2.45 | 1 |
10345 | TRDN | triadin | −2.45 | 1 |
158866 | ZDHHC15 | zinc finger, DHHC-type containing 15 | −2.44 | 1 |
55283 | MCOLN3 | mucolipin 3 | −2.42 | 1 |
653316 | FAM153C | family with sequence similarity 153, member C, pseudogene | −2.41 | 1 |
348158 | ACSM2B | acyl-CoA synthetase medium-chain family member 2B | −2.39 | 1 |
11227 | GALNT5 | polypeptide N-acetylgalactosaminyltransferase 5 | −2.39 | 1 |
3169 | FOXA1 | forkhead box A1 | −2.37 | 1 |
284716 | RIMKLA | ribosomal modification protein rimK-like family member A | −2.37 | 2 |
253559 | CADM2 | cell adhesion molecule 2 | −2.36 | 1 |
144453 | BEST3 | bestrophin 3 | −2.35 | 1 |
2258 | FGF13 | fibroblast growth factor 13 | −2.35 | 1 |
57863 | CADM3 | cell adhesion molecule 3 | −2.34 | 1 |
140456 | ASB11 | ankyrin repeat and SOCS box containing 11, E3 ubiquitin protein ligase | −2.32 | 2 |
346389 | MACC1 | metastasis associated in colon cancer 1 | −2.30 | 2 |
9378 | NRXN1 | neurexin 1 | −2.30 | 1 |
151887 | CCDC80 | coiled-coil domain containing 80 | −2.29 | 2 |
266977 | GPR110 | G protein-coupled receptor 110 | −2.28 | 1 |
3481 | IGF2 | insulin-like growth factor 2 | −2.27 | 1 |
57554 | LRRC7 | leucine rich repeat containing 7 | −2.27 | 1 |
80310 | PDGFD | platelet derived growth factor D | −2.25 | 1 |
342926 | ZNF677 | zinc finger protein 677 | −2.25 | 1 |
341640 | FREM2 | FRAS1 related extracellular matrix protein 2 | −2.24 | 1 |
5067 | CNTN3 | contactin 3 (plasmacytoma associated) | −2.22 | 1 |
4919 | ROR1 | receptor tyrosine kinase-like orphan receptor 1 | −2.20 | 1 |
948 | CD36 | CD36 molecule (thrombospondin receptor) | −2.19 | 1 |
23171 | GPD1L | glycerol-3-phosphate dehydrogenase 1-like | −2.18 | 1 |
64102 | TNMD | tenomodulin | −2.18 | 2 |
55638 | SYBU | syntabulin (syntaxin-interacting) | −2.17 | 1 |
6586 | SLIT3 | slit homolog 3 (Drosophila) | −2.13 | 2 |
2247 | FGF2 | fibroblast growth factor 2 (basic) | −2.11 | 1 |
115827 | RAB3C | RAB3C, member RAS oncogene family | −2.11 | 2 |
203859 | ANO5 | anoctamin 5 | −2.10 | 1 |
80110 | ZNF614 | zinc finger protein 614 | −2.10 | 1 |
115265 | DDIT4L | DNA-damage-inducible transcript 4-like | −2.03 | 1 |
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Oshima, S.; Asai, S.; Seki, N.; Minemura, C.; Kinoshita, T.; Goto, Y.; Kikkawa, N.; Moriya, S.; Kasamatsu, A.; Hanazawa, T.; et al. Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma. Int. J. Mol. Sci. 2021, 22, 6199. https://doi.org/10.3390/ijms22126199
Oshima S, Asai S, Seki N, Minemura C, Kinoshita T, Goto Y, Kikkawa N, Moriya S, Kasamatsu A, Hanazawa T, et al. Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2021; 22(12):6199. https://doi.org/10.3390/ijms22126199
Chicago/Turabian StyleOshima, Sachi, Shunichi Asai, Naohiko Seki, Chikashi Minemura, Takashi Kinoshita, Yusuke Goto, Naoko Kikkawa, Shogo Moriya, Atsushi Kasamatsu, Toyoyuki Hanazawa, and et al. 2021. "Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma" International Journal of Molecular Sciences 22, no. 12: 6199. https://doi.org/10.3390/ijms22126199