USP14 inhibition regulates tumorigenesis by inducing apoptosis in gastric cancer
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Deubiquitinases (DUBs) are an essential component of theubiquitin-proteasome system (UPS). They trim ubiquitin fromsubstrate proteins, thereby preventing them from degradation,and modulate different cellular processes. Ubiquitin-specificprotease 14 (USP14) is a DUB that has mainly been studied forits role in tumorigenesis in several cancers. In the present study,we found that the protein levels of USP14 were remarkablyhigher in gastric cancer tissues than in the adjacent normaltissues. We also demonstrated that the inhibition of USP14activity using IU1 (an USP14 inhibitor) or the inhibition ofUSP14 expression using USP14-specific siRNA markedly reducedthe viability of gastric cancer cells and suppressed their migratoryand invasive abilities. The reduction in gastric cancercell proliferation due to the inhibition of USP14 activity was aresult of the increase in the degree of apoptosis, as evidencedby the increased expression levels of cleaved caspase-3 andcleaved PARP. Furthermore, an experiment using the USP14inhibitor IU1 revealed that the inhibition of USP14 activitysuppressed 5-fluorouracil (5-FU) resistance in GC cells. Collectively,these findings indicate that USP14 plays critical roles ingastric cancer progression and suggest its potential to serve asa novel therapeutic target for gastric cancer treatment.
Abstract
Deubiquitinases (DUBs) are an essential component of theubiquitin-proteasome system (UPS). They trim ubiquitin fromsubstrate proteins, thereby preventing them from degradation,and modulate different cellular processes. Ubiquitin-specificprotease 14 (USP14) is a DUB that has mainly been studied forits role in tumorigenesis in several cancers. In the present study,we found that the protein levels of USP14 were remarkablyhigher in gastric cancer tissues than in the adjacent normaltissues. We also demonstrated that the inhibition of USP14activity using IU1 (an USP14 inhibitor) or the inhibition ofUSP14 expression using USP14-specific siRNA markedly reducedthe viability of gastric cancer cells and suppressed their migratoryand invasive abilities. The reduction in gastric cancercell proliferation due to the inhibition of USP14 activity was aresult of the increase in the degree of apoptosis, as evidencedby the increased expression levels of cleaved caspase-3 andcleaved PARP. Furthermore, an experiment using the USP14inhibitor IU1 revealed that the inhibition of USP14 activitysuppressed 5-fluorouracil (5-FU) resistance in GC cells. Collectively,these findings indicate that USP14 plays critical roles ingastric cancer progression and suggest its potential to serve asa novel therapeutic target for gastric cancer treatment.
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