OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma
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RESEARCH ARTICLE
Open Access
OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma Xiu-Ping Tu1†, Hao Li2,3,4†, Liang-Si Chen1, Xiao-Ning Luo1, Zhong-Ming Lu1, Si-Yi Zhang1* and Shao-Hua Chen1*
Abstract Background: Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. Methods: The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. Results: OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. Conclusions: Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC. Keywords: Orthodenticle homeobox 1, Laryngeal squamous cell carcinoma, MiR-129-5p, Tumor progression, Prognosis
Background Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant cancers to occur in the head and neck region. In China, the estimated incidence of LSCC was 26,400 new cases, while 14,500 related deaths occurred in 2015 [1]. In the United States, the incidence and mortality rates were 13,360 and 3660 per year in 2017, respctively [2]. Human papilloma virus infection, smoking, alcohol consumption and fried foods consumption * Correspondence: [email protected]; [email protected] † Xiu-Ping Tu and Hao Li contributed equally to this work. 1 Department of Otorhinolaryngology, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of China Full list of author information is available at the end of the article
are considered high-risk factors for the occurrence and development of laryngeal cancer [3–5]. At present, surgical resection, chemotherapy, and radiotherapy are considered the standard treatments for patients with LSCC [6, 7]. Despite advances in diagnosis and treatment, the prognosis of LSCC remains poor. Therefore, further understanding of the molecular mechanisms underlying the carcinogenesis and development of LSCC is important to identify new diagnostic markers and therapeutic targets for patients with LSCC. Orthodenticle homeobox 1 (OTX1)
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