Long noncoding RNA DUXAP8 contributes to the progression of hepatocellular carcinoma via regulating miR‐422a/PDK2 axis

• Published in: Cancer medicine (Malden, MA) MA), 2020-04, Vol.9 (7), p.2480-2490
• Main Authors: Wei, Feifei, Yang, Liang, Jiang, Dandan, Pan, Min, Tang, Guiyan, Huang, Mingyue, Zhang, Jing
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Biology; Cancer therapies; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell culture; Cell Proliferation; Cholecystokinin; DUXAP8; Female; Gastric cancer; Gene Expression Regulation, Neoplastic; HCC; Hepatocellular carcinoma; Homeobox; Humans; Kinases; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Lung cancer; Male; Medical prognosis; Medical research; Mesenchyme; Metastases; Metastasis; MicroRNAs; MicroRNAs - genetics; Middle Aged; miR‐422a; Mortality; Original Research; PDK2; Phenotypes; Plasmids; Prognosis; Proteins; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - genetics; Pyruvate Dehydrogenase Acetyl-Transferring Kinase - metabolism; Pyruvic acid; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Survival Rate; Tumor Cells, Cultured; Tumor suppressor genes; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2861

Background Hepatocellular carcinoma (HCC) is one of the most deadly cancer worldwide. Multiple long noncoding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the functon and mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in the progression of HCC. Methods Expression levels of DUXAP8 in HCC tissue samples were measured using qRT‐PCR. The association between pathological indexes and the expression of DUXAP8 was also analyzed. Human HCC cell lines SMMC‐7721 and QSG‐7701 were used in in vitro studies. CCK‐8 assay was used to assess the effect of DUXAP8 on HCC cell line proliferation. Scratch healing assay and Transwell assay were conducted to detect the effect of DUXAP8 on migration and invasion. Furthermore, dual‐luciferase reporter assay was used to confirm targeting relationship between miR‐422a and DUXAP8. Additionally, Western blot was used to detect the regulatory function of DUXAP8 on pyruvate dehydrogenase kinase 2 (PDK2). Results DUXAP8 expression HCC clinical samples was significantly increased and this was correlated with unfavorable pathological indexes. High expression of DUXAP8 was associated with shorter overall survival time of patients. Its overexpression remarkably facilitated the proliferation, metastasis, and epithelial‐mesenchymal transition of HCC cells. Accordingly, knockdown of it suppressed the malignant phenotypes of HCC cells. Overexpression of DUXAP8 significantly reduced the expression of miR‐422a by sponging it, but enhanced the expression of PDK2. Conclusions DUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA. DUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA.