Journal
AGING-US
Volume 10, Issue 11, Pages 3371-3381Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.101645
Keywords
hepatocellular carcinoma (HCC); long noncoding RNA (lncRNA); CDKN2BAS; ARHGAP18; miR-153-5p
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Funding
- Foundation of Wenling Municipal Science and Technology Project [2012WLCA0068]
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Background: Growing evidence shows that long noncoding RNAs (lncRNAs) play a crucial role in cancer progression. However, whether lncRNA CDKN2BAS is involved in human hepatocellular carcinoma (HCC) metastasis remains unclear. Methods: Human lncRNA microarray analysis was performed to detect differential expression levels of lncRNAs in metastatic HCC tissues. Effects of CDKN2BAS on cell proliferation, migration, and apoptosis were determined by MTT assay, colony formation assay, migration assay, scratch assay, and flow cytometry. The xenograft experiment was used to confirm the effect of CDKN2BAS on HCC in vivo. qRT-PCR and Western blot were performed to determine the expression levels of mRNAs and proteins. Luciferase reporter assay was used to identify the specific target relationships. Results: CDKN2BAS was remarkably up-regulated in metastatic HCC tissues compared with the adjacent nontumor tissues. CDKN2BAS promotes HCC cell growth and migration in vitro and in vivo. Additionally, CDKN2BAS upregulated the expression of Rho GTPase activating protein 18 (ARHGAP18) by sponging microRNA-153-5p (miR-153-5p), and thus promoted HCC cell migration. Besides, CDKN2BAS downregulated the expression of Kruppel-like factor 13 (KLF13) and activated MEK-ERK1/2 signaling, thus reducing apoptosis in HCC cells. Conclusions: Our study revealed that lncRNA CDKN2BAS promotes HCC metastasis by regulating the miR-1535p/ARHGAP18 signaling.
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