MiR-34c-3p targets Notch2 to inhibit cell invasion and epithelial-mesenchymal transition in nasopharyngeal carcinoma

Abstract

This study was to investigate role of miR-34c-3p/Notch2-EMT signal axis in Nasopharyngeal Carcinoma (NPC). Ten samples of NPC tissues and chronic inflammatory tissues of nasopharynx (CITN) were collected. 133 differentially expressed miRNAs, including 31 down-regulated and 102 up-regulated were identified in NPC tissues. MiR-34c-3p was down-regulated and Notch2 was up-regulated in NPC tissues compared with CITN tissues. MiR-34c-3p was overexpressed in 6-10B cells after transfected with miR-34c-3p mimic, while reduced in 5-8F cells after transfected with miR-34c-3p inhibitor. Notch2 was confirmed as a target gene of miR-34c-3p. miR-34c-3p overexpression in 6-10B cells suppressed, while knockdown in 5-8F cells promoted cell invasion ability. In molecular level, the expression of E-cadherin was increased, while N-cadherin was decreased after miR-34c-3p overexpression in 6-10B cells. Knockdown of miR-34c-3p obviously decreased E-cadherin, but increased N-cadherin expression in 5-8F cells. Targeting Notch2 by miR-34c-3p might be a promising target for NPS treatment.

Low levels of miR-34c in nasal washings as a candidate marker of aggressive disease in wood and leather exposed workers with sinonasal intestinal-type adenocarcinomas (ITACs)

“…Since the mucinous subtypes carry a poor prognosis [33] , it can be hypothesized that the downregulation of mir-34c may contribute to tumor aggressiveness. This is consistent with the tumor suppressive role of mir-34c against cancer cell growth, invasion, and metastasis by targeting Notch2, c-Met-and CDK1 [ [24] , [27] , [32] ].…”

“…MiR-34c is a recognized tumor suppressor able to inhibit cell migration and invasion in vitro and to prevent tumor growth and metastasis in an in vivo xenograft model of nasopharyngeal carcinoma [23] . Accordingly, mir-34c is down regulated in nasopharyngeal, laryngeal and lung cancers [ [24] , [25] , [26] , [27] , [28] , [29] ]. In addition, low mir-34c expression correlates with worse disease-free and overall survival in laryngeal and lung cancer patients [ [30] , [31] , [32] ] and with radioresistance [29] .…”