Abstract
BackgroundEpithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma (NPC).MethodsDifferentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, β-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/β-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed.ResultsThe has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, β-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions.ConclusionsmiR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/β-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC.Trial registrationChiCTR1800018889. Registered 15 October 2018.
Highlights
Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs
Results miR-506-3p and LIM Homeobox 2 (LHX2) are involved in nasopharyngeal carcinoma (NPC) A total of 4 NPC-related chip data, namely, GSE12425, GSE13597, GSE53819 and GSE64634 were screened using the Gene expression Omnibus (GEO) database for the identification of differentially expressed genes
The results indicated that solely the LHX2 gene was found at the intersection, with its high expression in NPC recorded in the four datasets
Summary
Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, derived from epithelial cells located in the nasopharynx, and is malignant in nature accompanied by early distant metastasis and local invasion, with a high incidence in southern China [1, 2]. The acquisition of metastatic potential in cancer cells including NPC cells, promotes the epithelial-mesenchymal transition (EMT), characterized by the loss of epithelial markers, the gain of mesenchymal markers as well as enhanced migration and invasion [7,8,9]. With a better understanding of the molecular mechanism controlling EMT process, targeting EMT multiple stages as a therapeutic target could benefit the treatment of epithelial malignancy and metastasis [10]
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