HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis

Abstract

HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.

Flotillin-2 promotes cell proliferation via activating the c-Myc/BCAT1 axis by suppressing miR-33b-5p in nasopharyngeal carcinoma

“…We explored the molecular mechanism of FLOT2 regulation of c-Myc in NPC cells. Generally, both transcriptional and post-transcriptional mechanisms can lead to fluctuation of mRNA levels [ 26 ]. Therefore, qPCR was used to detect the expression of c-Myc hnRNA in FLOT2 knockdown NPC cells using two sets of specific primers amplifying intron-1 and -2, respectively.…”

“…103 cases of paraffin-embedded and poorly differentiated squamous NPC tissue samples were collected from primary patients without any therapy during Jan 2010 to Dec 2012 in Xiangya Hospital of Central South University. The clinical stage of the patients was classified according to the seventh edition of AJCC guidelines as our previous illustration [ 26 ]. The patients uniformly received radiochemotherapy and the clinicopathological features, prognostic conditions of patients were retrospectively collected.…”

“…Human NPC cell lines, 5-8F and 6-10B, were cultured with RPMI-1640 medium (BI, Jerusalem, Israel) supplemented with 10% fetal bovine serum (BI, Jerusalem, Israel) as our previous description [ 13 , 26 ]. Stable cell lines, including 5-8F-shFLOT2, 5-8F-shBCAT1, 6-10B-FLOT2 and control cell lines, were previously established by us [ 13 , 25 , 31 ].…”

“…5-8F-shFLOT2+BCAT1 and 6-10B-FLOT2+shBCAT1 cell lines were constructed by infecting 5-8F-shFLOT2 and 6-10B-FLOT2 cells with lentivirus particles expressing BCAT1 and shBCAT1 (short hair BCAT1), respectively. The lentivirus expression plasmid pLV-puro-BCAT1 and pLV-U6-shBCAT1 were used to package lentiviral particles as our previous description [ 26 ]. MK2206 (Selleck, TX, USA) and BAY 11-7082 (Selleck, TX, USA) were added into the culture medium to inhibit the activities of AKT and NF-κB as indicated.…”

“…Plasmids, including pCMV-HA/c-Myc, pENTER-BCAT1 and control vectors, siRNAs (small inferring RNAs), including sic-Myc, siBCAT1 and siNC, miRNAs, including miR-33b-5p mimic, miR-33b-5p inhibitor and control miRNAs, were transfected into the corresponding cells as mentioned in manuscript using HighGene Transfection reagent (Abclonal, Wuhan, China) according to our previous description [ 26 ]. The siRNAs and miRNAs were purchased from Ribobio Inc. (Guangzhou, China).…”