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Cancers 2019, 11(2), 258; https://doi.org/10.3390/cancers11020258

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

1
Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan
2
Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
*
Author to whom correspondence should be addressed.
Received: 27 January 2019 / Revised: 18 February 2019 / Accepted: 18 February 2019 / Published: 22 February 2019
(This article belongs to the Special Issue MicroRNA-Associated Cancer Metastasis)
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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. View Full-Text
Keywords: microRNA; miR-451a; KIF2A; lung squamous cell carcinoma; antitumor microRNA; miR-451a; KIF2A; lung squamous cell carcinoma; antitumor
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Uchida, A.; Seki, N.; Mizuno, K.; Yamada, Y.; Misono, S.; Sanada, H.; Kikkawa, N.; Kumamoto, T.; Suetsugu, T.; Inoue, H. Regulation of KIF2A by Antitumor miR-451a Inhibits Cancer Cell Aggressiveness Features in Lung Squamous Cell Carcinoma. Cancers 2019, 11, 258.

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