Background: Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been reported to be a vital mediator in various cancers. But, in terms of gastric cancer (GC), the effects of UCA1 on GC cell proliferation, migration, invasion, and apoptosis remain unclear. This study aimed to uncover the potential regulatory mechanism of UCA1 in GC cells.
Methods: The expression level of UCA1 was first examined in the five different cell lines of HEK293, CCL-153, HUVEC, SUN-216, and SGC-7901 using a reverse-transcriptase quantitative polymerase chain reaction. Then, the vectors of short hairpin UCA1, the microRNA-182 (miR-182) mimic/inhibitor, and the pEX-tissue inhibitor of metalloproteinases 2 (TIMP2)/small interfering TIMP2 were transfected into SUN-216 and SGC-7901 cells to alter UCA1, miR-182, and TIMP2 expression. To investigate the biological functions, cell viability, migration, invasion, and apoptosis were examined by Cell Counting Kit-8, Transwell, and flow cytometry. The key factors of apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) and nuclear factor κB (NF-κB) signal pathways were determined by Western blot analysis.
Results: UCA1 was upregulated in SUN-216 and SGC-7901 cells than in the other three cell lines of HEK293, CCL-153, and HUVEC. Knockdown of UCA1 significantly suppressed cell viability, migration, and invasion, and promoted apoptosis by regulating B-cell lymphoma 2, Bax, and cleaved-caspase-3/9 expressions. However, miR-182 overexpression markedly reversed the regulatory effect of UCA1 knockdown on SUN-216 and SGC-7901 cells. TIMP2 was a direct target gene of miR-182, and TIMP2 overexpression exhibited the same effect of UCA1 knockdown on cell viability, migration, invasion, and apoptosis. Besides, miR-182 activated PI3K/AKT/GSK3β and NF-κB signal pathways by regulation of TIMP2.
Conclusion: Knockdown of UCA1 exerts an anticancer effect on GC cells by regulating miR-182.
Keywords: gastric cancer; microRNA-182; nuclear factor κB; phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 β; tissue inhibitor of metalloproteinases 2; urothelial carcinoma-associated 1.
© 2018 Wiley Periodicals, Inc.