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

Abstract

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.

LncRNA RUSC1-AS1 promotes the proliferation of hepatocellular carcinoma cells through modulating NOTCH signaling

“…LncRNA OIP5-AS1 endogenously sponges miR-363-3p to up-regulate SOX4, thus contributing to HCC progression [30]. LncRNA DUXAP8 facilitates HCC cell proliferation, migration and invasion via modulation on miR-422a/PDK2 axis [31]. In present study, we identified that RUSC1-AS1 could bind with hsa-miR-7-5p.…”

Clinical significance of long non-coding RNA DUXAP8 and its protein coding genes in hepatocellular carcinoma

“…Our study identified three potential drugs targeting DUXAP8 in HCC. Although several related studies focusing on DUXAP8 in HCC were previously reported 63 - 65 , our study has several main findings that could distinguished from them, such as in both diagnostic and prognostic significance of DUXAP8 and it-related PCGs, construction of risk score model and nomogram, potential target drugs toward DXUAP8 aspects.…”

MicroRNA‑422a functions as a tumor suppressor in glioma by regulating the Wnt/β‑catenin signaling pathway via RPN2

“…Zhou et al (49), demonstrated that lncRNAD63785 acts as a ceRNA of miR-422a and enhances chemoresistance by retarding miR-422a-dependent suppression of MEF2D. However, more circRNAs or lncRNAs sponging miR-422a have been identified and validated (50,51), which may be of significance in understanding the in-depth molecular mechanism of glioma initiation and progression, and combined treatment responses.…”