Overexpression of hsa‑miR‑125a‑5p enhances proliferation, migration and invasion of head and neck squamous cell carcinoma cell lines by upregulating C‑C chemokine receptor type 7

Jin,Shan; Liu,Min‑Da; Wu,Hong; Pang,Pai; Wang,Song; Li,Zhen‑Ning; Sun,Chang‑Fu; Liu,Fa‑Yu

doi:10.3892/ol.2018.8564

Overexpression of hsa‑miR‑125a‑5p enhances proliferation, migration and invasion of head and neck squamous cell carcinoma cell lines by upregulating C‑C chemokine receptor type 7

Authors:
- Shan Jin
- Min‑Da Liu
- Hong Wu
- Pai Pang
- Song Wang
- Zhen‑Ning Li
- Chang‑Fu Sun
- Fa‑Yu Liu
View Affiliations

Affiliations: Department of Oromaxillofacial‑Head and Neck Surgery, Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, P.R. China
Published online on: April 25, 2018 https://doi.org/10.3892/ol.2018.8564
Pages: 9703-9710
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Head and neck squamous cell carcinoma (HNSCC) is usually diagnosed accompanied by lymph node metastasis. C‑C chemokine receptor type 7 (CCR7) is associated with the invasion and metastasis of tumors in HNSCC through various signaling pathways. The role of hsa‑miR‑125a‑5p in HNSCC remains unclear. The present study was performed to investigate the association between hsa‑miR‑125a‑5p and CCR7 in HNSCC. Reverse transcription‑quantitative polymerase chain reaction was applied to analyze the expression of hsa‑miR‑125a‑5p in clinical samples. Cell Counting Kit‑8, Transwell and wound healing assays were used to detect cell proliferation, invasion, and metastasis, respectively, following overexpression of hsa‑miR‑125a‑5p. Changes in protein expression of CCR7 were observed using western blotting. In the survival analysis, Student's t‑tests and log rank tests were performed to analyze the association between the expression of hsa‑miR‑125a‑5p, and HNSCC according to the Cancer Genome Atlas database. The expression of hsa‑miR‑125a‑5p was identified to be significantly lower in cancer tissue compared with the corresponding adjacent normal tissues in clinical samples (P=0.038). The results of western blotting indicated that there was a positive regulatory association between hsa‑miR‑125a‑5p and CCR7. Furthermore, overexpression of hsa‑miR‑125a‑5p significantly enhanced the ability of cell proliferation, migration and invasion in HNSCC, with upregulation of CCR7. The results of survival analysis revealed that patients in the low expression group of hsa‑miR‑125a‑5p tended to have longer survival times compared with the high expression group (P=0.045). Altogether, the data raised the possibility that hsa‑miR‑125a‑5p has a significant role in promoting cancer in HNSCC, which may provide a basis for the treatment of HNSCC in molecular targeted therapy. Further studies are required to ascertain the role of hsa‑miR‑125a‑5p in other HNSCC cell lines and in vivo.

View Figures

View References

1	Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI
2	Dünne AA, Müller HH, Eisele DW, Kessel K, Moll R and Werner JA: Meta-analysis of the prognostic significance of perinodal spread in head and neck squamous cell carcinomas (HNSCC) patients. Eur J Cancer. 42:1863–1868. 2006. View Article : Google Scholar : PubMed/NCBI
3	Xing Y, Zhang J, Lin H, Gold KA, Sturgis EM, Garden AS, Lee JJ and William WN Jr: Relation between the level of lymph node metastasis and survival in locally advanced head and neck squamous cell carcinoma. Cancer. 122:534–545. 2015. View Article : Google Scholar : PubMed/NCBI
4	Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, et al: International union of basic and clinical pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev. 66:1–79. 2013. View Article : Google Scholar : PubMed/NCBI
5	Yang J, Wang S, Zhao G and Sun B: Effect of chemokine receptors CCR7 on disseminated behavior of human T cell lymphoma: Clinical and experimental study. J Exp Clin Cancer Res. 30:512011. View Article : Google Scholar : PubMed/NCBI
6	Förster R, Schubel A, Breitfeld D, Kremmer E, Renner-Müller I, Wolf E and Lipp M: CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. Cell 1999.99: 23–33. J Immunol. 196:5–15. 2016.PubMed/NCBI
7	Wang J, Xi L, Hunt JL, Gooding W, Whiteside TL, Chen Z, Godfrey TE and Ferris RL: Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype. Cancer Res. 64:1861–1866. 2004. View Article : Google Scholar : PubMed/NCBI
8	Liu FY, Safdar J, Li ZN, Fang QG, Zhang X, Xu ZF and Sun CF: CCR7 regulates cell migration and invasion through MAPKs in metastatic squamous cell carcinoma of head and neck. Int J Oncol. 45:2502–2510. 2014. View Article : Google Scholar : PubMed/NCBI
9	Zhao ZJ, Liu FY, Li P, Ding X, Zong ZH and Sun CF: CCL19-induced chemokine receptor 7 activates the phosphoinositide-3 kinase-mediated invasive pathway through Cdc42 in metastatic squamous cell carcinoma of the head and neck. Oncol Rep. 25:729–737. 2011.PubMed/NCBI
10	Chekulaeva M and Filipowicz W: Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol. 21:452–460. 2009. View Article : Google Scholar : PubMed/NCBI
11	Ambros V and Lee RC: Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. Methods Mol Biol. 265:131–158. 2004.PubMed/NCBI
12	Volinia S, Galasso M, Sana ME, Wise TF, Palatini J, Huebner K and Croce CM: Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci USA. 109:3024–3029. 2012. View Article : Google Scholar : PubMed/NCBI
13	Olena AF and Patton JG: Genomic organization of microRNAs. J Cell Physiol. 222:540–545. 2010.PubMed/NCBI
14	Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E and Wong DT: Salivary microRNA: Discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res. 15:5473–5477. 2009. View Article : Google Scholar : PubMed/NCBI
15	Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y and Mori M: MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. Clin Cancer Res. 17:2725–2733. 2011. View Article : Google Scholar : PubMed/NCBI
16	Janiszewska J, Szaumkessel M and Szyfter K: MicroRNAs are important players in head and neck carcinoma: A review. Crit Rev Oncol Hematol. 88:716–728. 2013. View Article : Google Scholar : PubMed/NCBI
17	National Comprehensive Cancer Network, . Head and Neck Cancer. (Version 1.2017). https://www.nccn.org/professionals/physician_gls/#siteFebruary 1–2017
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Okamoto K, Miyoshi K and Murawaki Y: miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells. PloS One. 8:e776232013. View Article : Google Scholar : PubMed/NCBI
20	Volinia S, Galasso M, Costinean S, Tagliavini L, Gamberoni G, Drusco A, Marchesini J, Mascellani N, Sana ME, Jarour Abu R, et al: Reprogramming of miRNA networks in cancer and leukemia. Genome Res. 20:589–599. 2010. View Article : Google Scholar : PubMed/NCBI
21	Liang Y, Ridzon D, Wong L and Chen C: Characterization of microRNA expression profiles in normal human tissues. BMC Genomics. 8:1662007. View Article : Google Scholar : PubMed/NCBI
22	Ramdas L, Giri U, Ashorn CL, Coombes KR, El-Naggar A, Ang KK and Story MD: MiRNA expression profiles in head and neck squamous cell carcinoma and adjacent normal tissue. Head Neck. 31:642–654. 2009. View Article : Google Scholar : PubMed/NCBI
23	Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, Perez-Ordonez B, Jurisica I, O'Sullivan B, Waldron J, et al: Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 16:1129–1139. 2010. View Article : Google Scholar : PubMed/NCBI
24	Jiang L, Huang Q, Zhang S, Zhang Q, Chang J, Qiu X and Wang E: Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells. BMC Cancer. 10:3182010. View Article : Google Scholar : PubMed/NCBI
25	Tiwari A, Shivananda S, Gopinath KS and Kumar A: MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor alpha: Implications for cancer therapeutics. J Biol Chem. 289:32276–32290. 2014. View Article : Google Scholar : PubMed/NCBI
26	Liu FY, Safdar J, Li ZN, Fang QG, Zhang X, Xu ZF and Sun CF: CCR7 regulates cell migration and invasion through JAK2/STAT3 in metastatic squamous cell carcinoma of the head and neck. Biomed Res Int. 2014:4153752014. View Article : Google Scholar : PubMed/NCBI
27	Guo N, Liu F, Yang L, Huang J, Ding X and Sun C: Chemokine receptor 7 enhances cell chemotaxis and migration of metastatic squamous cell carcinoma of head and neck through activation of matrix metalloproteinase-9. Oncol Rep. 32:794–800. 2014. View Article : Google Scholar : PubMed/NCBI
28	Brennecke J, Stark A, Russell RB and Cohen SM: Principles of microRNA-target recognition. PLoS Biol. 3:e852005. View Article : Google Scholar : PubMed/NCBI
29	Yuan J, Xiao G, Peng G, Liu D, Wang Z, Liao Y, Liu Q, Wu M and Yuan X: MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ. Biochem Biophys Res Commun. 457:171–176. 2015. View Article : Google Scholar : PubMed/NCBI
30	Khan AA, Betel D, Miller ML, Sander C, Leslie CS and Marks DS: Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs. Nat Biotechnol. 27:549–555. 2009. View Article : Google Scholar : PubMed/NCBI
31	Ørom UA, Nielsen FC and Lund AH: MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 30:460–471. 2008. View Article : Google Scholar : PubMed/NCBI