Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma.

Akifumi Uchida,Hiroki Sanada,Takayuki Suetsugu,Tomohiro Kumamoto,Keiko Mizuno,Shunsuke Misono,Naohiko Seki,Naoko Kikkawa,Hiromasa Inoue,Yasutaka Yamada

doi:10.3390/cancers11020258

Akifumi Uchida, Hiroki Sanada + Show 8 more

Open Access

https://doi.org/10.3390/cancers11020258

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Journal: Cancers	Publication Date: Feb 22, 2019
Citations: 26	License type: CC BY 4.0

Affiliation: Kagoshima University, Chiba University

Abstract

In the human genome, miR-451a is encoded close to the miR-144 on chromosome region 17q11.2. Our previous study showed that both strands of pre-miR-144 acted as antitumor miRNAs and were involved in lung squamous cell carcinoma (LUSQ) pathogenesis. Here, we aimed to investigate the functional significance of miR-451a and to identify its targeting of oncogenic genes in LUSQ cells. Downregulation of miR-451a was confirmed in LUSQ clinical specimens, and low expression of miR-451a was significantly associated with poor prognosis of LUSQ patients (overall survival: p = 0.035, disease-free survival: p = 0.029). Additionally, we showed that ectopic expression of miR-451a significantly blocked cancer cell aggressiveness. In total, 15 putative oncogenic genes were shown to be regulated by miR-451a in LUSQ cells. Among these targets, high kinesin family member 2A (KIF2A) expression was significantly associated with poor prognosis (overall survival: p = 0.043, disease-free survival: p = 0.028). Multivariate analysis showed that KIF2A expression was an independent prognostic factor in patients with LUSQ (hazard ratio = 1.493, p = 0.034). Aberrant KIF2A expression promoted the malignant transformation of this disease. Analytic strategies based on antitumor miRNAs and their target oncogenes are effective tools for identification of novel molecular pathogenesis of LUSQ.

Highlights

Lung cancer is the most common cause of cancer-related death worldwide, accounting for more than 1.7 million deaths each year [1]
To further confirm the role of in the pathogenesis of lung squamous cell carcinoma (LUSQ), we evaluated the effects of EBC-1 and SK-MES-1 cells using small interfering of kinesin family member 2A (KIF2A) downregulation in EBC-1 and SK-MES-1 cells using small interfering RNAs
We focused on KIF2A because its expression was significantly associated with a worse prognosis for patients with LUSQ

Summary

Introduction

Lung cancer is the most common cause of cancer-related death worldwide, accounting for more than 1.7 million deaths each year [1]. The most common type of lung cancer is non-small cell lung cancer (NSCLC), which can be divided into several subtypes, including squamous cell carcinoma (LUSQ), adenocarcinoma (LUAD), and large cell carcinoma [2]. Patients with LUAD show improved survival rates following treatment with epidermal growth factor receptor tyrosine kinase inhibitors, anaplastic lymphoma kinase tyrosine kinase inhibitors, and immune checkpoint inhibitors [3,4,5,6]. LUSQ remains a common cancer among NSCLCs, and over 400,000 people worldwide are diagnosed with LUSQ each year [7]. The majority of patients with LUSQ have a history of heavy smoking, highlighting tobacco-related carcinogenesis as a clear causative factor of LUSQ.

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