Abstract
BackgroundHepatocellular 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.MethodsExpression 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).ResultsDUXAP8 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.ConclusionsDUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA.
Highlights
Hepatocellular carcinoma (HCC) is one of the common tumors of the digestive system
LncRNA HOTAIR is highly expressed in lung cancer, and its high expression is significantly associated with lung cancer metastasis and poor prognosis 8; long noncoding RNAs (lncRNAs) PVT1 is upregulated in gastric cancer tissues, and its overexpression enhances the cancer cell proliferation and invasion, which is significantly associated with poor prognosis.[9]
GAS5 is downregulated in HCC, and its overexpression can impede cell migration and invasion 25; the expression of lncRNA HOTAIR in HCC is elevated, and patients with high expression of it have a poor prognosis 26; the expression of lncRNA MALAT1 is confirmed to be an independent prognostic factor for HCC.[10]
Summary
Hepatocellular carcinoma (HCC) is one of the common tumors of the digestive system. Its high incidence and high mortality rate make it one of the major health threats in China.[1,2] Because HCC patients are asymptomatic in the early stage, most of them are diagnosed at an advanced stage with high mortality and low survival rate.[3]. MiRNA regulates the expression of related genes at the post-transcription or translation, which is at play in the process of tumorigenesis, development, and metastasis.[15,16,17] Accumulating studies in the past decades have proved that miRNAs can act as tumor suppressors or cancer-promoting factors in the development of HCC.[18,19] miR-422a is abnormally expressed in colorectal cancer, glioma, head and neck squamous cell carcinoma, and counts in the proliferation and metastasis of cancer cells.[20,21,22] Importantly, miR-422a is downregulated in HCC, and overexpression can significantly inhibit the malignant phenotypes of HCC cells.[23] While the mechanism of miR-422a dysregulation in HCC needs further investigation. We confirmed that DUXAP8 could promote the development of HCC cells by modulating miR-422a/pyruvate dehydrogenase kinase 2 (PDK2)
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