Involvement of the Wnt/&beta;‑Catenin signaling pathway in the heterogenous nuclear ribonucleoprotein&nbsp;K‑driven inhibition of proliferation and migration in head and neck squamous cell carcinoma

Liu,Hongfei; Chen,Xiaohong; Yang,Xingjiu; Li,Mengyuan; Zhang,Wenlong; Zhang,Guoxin; Zhan,Xiangwen; Cao,Lin; Li,Weisha; Huang,Zhigang; Gao,Ran

doi:10.3892/ol.2020.12257

Involvement of the Wnt/β‑Catenin signaling pathway in the heterogenous nuclear ribonucleoprotein K‑driven inhibition of proliferation and migration in head and neck squamous cell carcinoma

Authors:
- Hongfei Liu
- Xiaohong Chen
- Xingjiu Yang
- Mengyuan Li
- Wenlong Zhang
- Guoxin Zhang
- Xiangwen Zhan
- Lin Cao
- Weisha Li
- Zhigang Huang
- Ran Gao
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Affiliations: Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China, NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100021, P.R. China
Published online on: October 29, 2020 https://doi.org/10.3892/ol.2020.12257
Article Number: 394
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The abnormal upregulation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) expression levels were reported to be involved in the progression of various types of cancer. Therefore, it is hypothesized that hnRNP K may serve as a useful diagnostic marker and antitumor target; however, only a few studies to date have investigated the exact role of hnRNP K in head and neck squamous cell carcinoma (HNSCC) and the potential downstream signaling pathway involved. The present study aimed to identify the roles of hnRNP K in the proliferation and migration of HNSCC, and the possible signaling pathways hnRNP K may be associated with in HNSCC. hnRNP K expression levels in clinical HNSCC samples were analyzed using the Oncomine and UALCAN databases, and its association with the survival of patients with HNSCC was analyzed using the tumor‑immune system interactions database. Short hairpin RNA targeting hnRNP K was transfected into the CAL‑27 cell line to establish HNSCC cells with stable hnRNP K‑knockdown. Cell viability was analyzed using a Cell Counting Kit‑8 assay and an absolute count assay, and cell proliferation was measured using 5‑ethynyl‑2'‑deoxyuridine incorporation and colony formation assays. Migratory ability of cells was analyzed using wound healing assay and transwell assay. The growth of xenografts derived from hnRNP K‑knockdown cells was also evaluated, and bioinformatics analyses were performed using the Gene Ontology and Kyoto Encyclopedia for Genes and Genomes databases to determine the possible downstream signaling pathways of hnRNP K. Furthermore, the status of the Wnt/β‑Catenin signaling pathway in hnRNP K‑knockdown cells mediated by small interfering RNA was determined using reverse transcription‑quantitative PCR and western blotting. The results revealed that the expression levels of hnRNP K were upregulated in HNSCC cell lines and tissues. Moreover, the upregulation of hnRNP K expression levels was associated with poor survival of patients with HNSCC. The knockdown of hnRNP K also decreased HNSCC cell proliferation and migration, and inhibited tumor growth in nude mice. Bioinformatics analyses identified the Wnt/β‑Catenin signaling pathway as a possible downstream signaling pathway of hnRNP K. Knockdown of hnRNP K significantly downregulated the expression levels of Wnt/β‑Catenin signaling pathway‑related proteins; while with knockdown of hnRNP K and overexpression of β‑Catenin, the expression levels of Wnt/β‑Catenin signaling pathway‑related proteins were partially rescued. In conclusion, the present findings indicated that hnRNP K may serve as a candidate diagnostic biomarker and a promising therapeutic target for HNSCC.

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