BackgroundOral squamous cell carcinoma (OSCC) is a malignant tumor that may occur anywhere within the oral cavity. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. We investigated the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in OSCC cells treated with bortezomib (a proteasome inhibitor) combined with irradiation (IR) treatment.MethodsThe effects of combined treatment in OSCC cells were investigated using assays of cell viability, autophagy, apoptosis, western blotting, and immunofluorescence staining. The ubiquitination of proteins was analyzed by immunoprecipitation. Stable knockdown of TRAF6 in OSCC cells was constructed with lentivirus. The xenograft murine models were used to observe tumor growth.ResultsWe found synergistic effects of bortezomib and IR on the viability of human oral cancer cells. The combination of bortezomib and IR treatment induced autophagic cell death. Furthermore, bortezomib inhibited IR-induced TRAF6 ubiquitination and inhibited TRAF6-mediated Akt activation. Bortezomib reduced TRAF6 protein expression through autophagy-mediated lysosomal degradation. TRAF6 played an oncogenic role in tumorigenesis of human oral cancer cells and oral tumor growth was suppressed by bortezomib and IR treatment. In addition, OSCC patients with expression of TRAF6 showed a trend towards poorer cancer-specific survival when compared with patients without TRAF6 expression.ConclusionsA combination of a proteasome inhibitor, IR treatment and TRAF6 inhibition could be a novel therapeutic strategy in OSCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0760-0) contains supplementary material, which is available to authorized users.

Antisense non-coding RNA in the INK4A locus (ANRIL) has been recognized as a cancer-related lncRNA in hepatocellular carcinoma previously. This study aimed to reveal the functional effects and mechanisms of ANRIL on hepatocellular carcinoma cells in vitro. The expression of ANRIL in hepatocellular carcinoma cell lines (MHCC97 and Li-7) and non-tumourigenic liver cell line THLE-3 was detected by qRT-PCR. The expression of ANRIL, miR-144 and PBX3 in hepatocellular carcinoma cells was altered simultaneously or respectively by vector/oligonucleotide transfection. Then, cell viability, migration, invasion, apoptotic cell rate, protein expression of apoptosis-related factors were assessed. The correlation between ANRIL, miR-144 and PBX3 was explored. ANRIL was highly expressed in MHCC97 and Li-7 cells when compared to THLE-3 cells. ANRIL overexpression promoted cell viability, migration, invasion and suppressed apoptosis of MHCC97 and Li-7 cells. ANRIL negatively regulated miR-144, and oncogenic effects of ANRIL were attenuated when miR-144 was overexpressed. PBX3 was a direct target of miR-144. miR-144 overexpression blocked PI3K/AKT and JAK/STAT signalling pathways via targeting PBX3. Our data documented that ANRIL promoted hepatocellular carcinoma cells growth, migration and invasion. One of the possible mechanisms responsible for the tumour-promoting actions is that ANRIL sponging miR-144 to derepress PBX3.

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