Identification of miR-199-5p and miR-199-3p Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Identification of Putative Targets Controlled by miR-199-5p and miR-199-3p in HNSCC Cells
2.2. Gene set Enrichment Analysis (GSEA)
2.3. HNSCC Cell Lines
2.4. Transfection of Mature miRNAs and Small-Interfering RNAs (siRNAs) into HNSCC Cells
2.5. RNA Extraction and Quantitative Reverse-Transcription PCR (qRT-PCR)
2.6. Immunohistochemistry
2.7. Western Blotting
2.8. Dual Luciferase Reporter Assays
2.9. Cell Proliferation, Migration, and Invasion Assays in HNSCC Cells
2.10. Statistical Analysis
3. Results
3.1. Identification of miR-199-5p and miR-199-3p Coordinately Regulated Genes in HNSCC Cells
3.2. Expression and Clinical Significance of the Putative Target Genes in Patients with HNSCC according to TCGA Analysis
3.3. FXR1- and PXN-Mediated Pathways in HNSCC Cells
3.4. Expression of PXN in HNSCC Clinical Specimens
3.5. Regulation of PXN Expression by miR-199-5p and miR-199-3p in HNSCC Cells
3.6. Effects of PXN Knockdown on the Proliferation, Invasion and Migration of HNSCC Cells
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Entrez Gene ID | Gene Symbol | Gene Name | miR-199-5p Total Conserved Sites | miR-199-3p Total Conserved Sites |
---|---|---|---|---|
19 | ABCA1 | ATP-binding cassette, sub-family A (ABC1), member 1 | 1 | 1 |
340485 | ACER2 | alkaline ceramidase 2 | 1 | 1 |
92 | ACVR2A | activin A receptor, type IIA | 1 | 2 |
93 | ACVR2B | activin A receptor, type IIB | 3 | 1 |
57188 | ADAMTSL3 | ADAMTS-like 3 | 1 | 3 |
120 | ADD3 | adducin 3 (γ) | 1 | 1 |
157 | ADRBK2 | adrenergic, beta, receptor kinase 2 | 1 | 1 |
81573 | ANKRD13C | ankyrin repeat domain 13C | 1 | 1 |
283373 | ANKRD52 | ankyrin repeat domain 52 | 1 | 1 |
57569 | ARHGAP20 | Rho GTPase activating protein 20 | 1 | 1 |
23365 | ARHGEF12 | Rho guanine nucleotide exchange factor (GEF) 12 | 1 | 1 |
222255 | ATXN7L1 | ataxin 7-like 1 | 1 | 1 |
27443 | CECR2 | cat eye syndrome chromosome region, candidate 2 | 2 | 1 |
10659 | CELF2 | CUGBP, Elav-like family member 2 | 1 | 2 |
387119 | CEP85L | centrosomal protein 85kDa-like | 1 | 1 |
153222 | CREBRF | CREB3 regulatory factor | 1 | 1 |
51232 | CRIM1 | cysteine rich transmembrane BMP regulator 1 (chordin-like) | 1 | 1 |
1496 | CTNNA2 | catenin (cadherin-associated protein), α2 | 1 | 1 |
84301 | DDI2 | DNA-damage inducible 1 homolog 2 (S. cerevisiae) | 1 | 1 |
55789 | DEPDC1B | DEP domain containing 1B | 1 | 1 |
2066 | ERBB4 | v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4 | 1 | 2 |
55137 | FIGN | fidgetin | 1 | 1 |
23767 | FLRT3 | fibronectin leucine rich transmembrane protein 3 | 1 | 1 |
10690 | FUT9 | fucosyltransferase 9 (α (1,3) fucosyltransferase) | 1 | 1 |
8087 | FXR1 | fragile X mental retardation, autosomal homolog 1 | 2 | 1 |
2651 | GCNT2 | glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (I blood group) | 1 | 1 |
54891 | INO80D | INO80 complex subunit D | 1 | 1 |
3675 | ITGA3 | integrin, α3 (antigen CD49C, α 3 subunit of VLA-3 receptor) | 1 | 1 |
8516 | ITGA8 | integrin, α8 | 1 | 1 |
11278 | KLF12 | Kruppel-like factor 12 | 1 | 1 |
26249 | KLHL3 | kelch-like family member 3 | 1 | 3 |
84458 | LCOR | ligand dependent nuclear receptor corepressor | 2 | 2 |
10960 | LMAN2 | lectin, mannose-binding 2 | 1 | 1 |
84061 | MAGT1 | magnesium transporter 1 | 1 | 1 |
4217 | MAP3K5 | mitogen-activated protein kinase 5 | 1 | 1 |
5599 | MAPK8 | mitogen-activated protein kinase 8 | 1 | 1 |
90411 | MCFD2 | multiple coagulation factor deficiency 2 | 1 | 1 |
54842 | MFSD6 | major facilitator superfamily domain containing 6 | 1 | 1 |
51701 | NLK | nemo-like kinase | 3 | 1 |
57532 | NUFIP2 | nuclear fragile X mental retardation protein interacting protein 2 | 1 | 1 |
10298 | PAK4 | p21 protein (Cdc42/Rac)-activated kinase 4 | 1 | 2 |
27253 | PCDH17 | protocadherin 17 | 1 | 1 |
5150 | PDE7A | phosphodiesterase 7A | 1 | 1 |
57475 | PLEKHH1 | pleckstrin homology domain containing, family H (with MyTH4 domain) member 1 | 1 | 1 |
5495 | PPM1B | protein phosphatase, Mg2+/Mn2+ dependent, 1B | 1 | 1 |
55607 | PPP1R9A | protein phosphatase 1, regulatory subunit 9A | 1 | 1 |
63976 | PRDM16 | PR domain containing 16 | 1 | 1 |
5813 | PURA | purine-rich element binding protein A | 1 | 1 |
5829 | PXN | paxillin | 1 | 1 |
5925 | RB1 | retinoblastoma 1 | 1 | 1 |
54502 | RBM47 | RNA binding motif protein 47 | 1 | 1 |
5991 | RFX3 | regulatory factor X, 3 (influences HLA class II expression) | 1 | 1 |
6096 | RORB | RAR-related orphan receptor B | 1 | 2 |
9644 | SH3PXD2A | SH3 and PX domains 2A | 1 | 1 |
25769 | SLC24A2 | solute carrier family 24 (sodium/potassium/calcium exchanger), member 2 | 1 | 1 |
8303 | SNN | stannin | 1 | 1 |
6667 | SP1 | Sp1 transcription factor | 1 | 1 |
257397 | TAB3 | TGF-β activated kinase 1/MAP3K7 binding protein 3 | 1 | 1 |
57551 | TAOK1 | TAO kinase 1 | 1 | 2 |
10099 | TSPAN3 | tetraspanin 3 | 1 | 1 |
57695 | USP37 | ubiquitin specific peptidase 37 | 1 | 1 |
23063 | WAPAL | wings apart-like homolog (Drosophila) | 1 | 2 |
10472 | ZBTB18 | zinc finger and BTB domain containing 18 | 1 | 2 |
26137 | ZBTB20 | zinc finger and BTB domain containing 20 | 2 | 2 |
6935 | ZEB1 | zinc finger E-box binding homeobox 1 | 1 | 1 |
80139 | ZNF703 | zinc finger protein 703 | 1 | 1 |
374655 | ZNF710 | zinc finger protein 710 | 1 | 1 |
283337 | ZNF740 | zinc finger protein 740 | 1 | 1 |
A. Significantly Enriched Gene Sets in the High FXR1 Expression Group | ||
---|---|---|
Name | Normalized Enrichment Score | FDR q-Value |
KEGG_Cardiac muscle contraction | 2.009 | 0.001 |
KEGG_Dilated cardiomyopathy | 1.968 | 0.001 |
KEGG_Hypertrophic cardiomyopathy HCM | 1.929 | 0.003 |
KEGG_Maturity onset diabetes of the young | 1.918 | 0.002 |
B. Significantly enriched gene sets in the high PXN expression group | ||
Name | normalized enrichment score | FDR q-value |
KEGG_Focal adhesion | 2.458 | q < 0.001 |
KEGG_ECM receptor interaction | 2.316 | q < 0.001 |
KEGG_Cytosolic DNA sensing pathway | 2.117 | 0.001 |
KEGG_Proteosome | 2.029 | 0.003 |
KEGG_Hypetrophic cardiomyopathy HCM | 1.995 | 0.005 |
KEGG_NOD-like receptor signaling pathway | 1.896 | 0.009 |
KEGG_Viral myocarditis | 1.894 | 0.008 |
KEGG_Dilated Cardiomyopathy | 1.804 | 0.014 |
KEGG_Bladder cancer | 1.784 | 0.016 |
KEGG_Cytokine cytokine receptor interaction | 1.776 | 0.016 |
KEGG_JAK/STAT signaling pathway | 1.712 | 0.026 |
KEGG_RIG-I-like receptor signaling pathway | 1.673 | 0.033 |
KEGG_Small cell lung cancer | 1.644 | 0.038 |
KEGG_Arryhythmogenic right ventricular cardiomyopathy ARVC | 1.639 | 0.037 |
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Tanaka, N.; Minemura, C.; Asai, S.; Kikkawa, N.; Kinoshita, T.; Oshima, S.; Koma, A.; Kasamatsu, A.; Hanazawa, T.; Uzawa, K.; et al. Identification of miR-199-5p and miR-199-3p Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma. Genes 2021, 12, 1910. https://doi.org/10.3390/genes12121910
Tanaka N, Minemura C, Asai S, Kikkawa N, Kinoshita T, Oshima S, Koma A, Kasamatsu A, Hanazawa T, Uzawa K, et al. Identification of miR-199-5p and miR-199-3p Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma. Genes. 2021; 12(12):1910. https://doi.org/10.3390/genes12121910
Chicago/Turabian StyleTanaka, Nozomi, Chikashi Minemura, Shunichi Asai, Naoko Kikkawa, Takashi Kinoshita, Sachi Oshima, Ayaka Koma, Atsushi Kasamatsu, Toyoyuki Hanazawa, Katsuhiro Uzawa, and et al. 2021. "Identification of miR-199-5p and miR-199-3p Target Genes: Paxillin Facilities Cancer Cell Aggressiveness in Head and Neck Squamous Cell Carcinoma" Genes 12, no. 12: 1910. https://doi.org/10.3390/genes12121910