Long Non-Coding RNA DUXAP8 Enhances Renal Cell Carcinoma Progression via Downregulating miR-126

Huang, Tao; Wang, Xiao; Yang, Xiaokun; Ji, Jianlei; Wang, Qinghai; Xuan, Yue; Zheng, Dong

doi:10.12659/msm.910054

Cited by 50 publications

(54 citation statements)

References 27 publications

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“…Increasing studies have shown that lncRNA can repress miRNAs as competitive endogenous RNAs (ceRNAs). It is reported that DUXAP8 can act as a ceRNA of miR‐577 to promote the expression of RAB14, thus promoting the migration and invasion of colorectal cancer cells ; in renal cell carcinoma, DUXAP8 targets miR‐126 and promotes cancer progression . Based on the difference in the expression and role of DUXAP8 and miR‐422a in HCC, we speculated that there was a regulatory relationship between them.…”

Section: Discussionmentioning

confidence: 97%

“…It is reported that DUXAP8 can act as a ceRNA of miR-577 to promote the expression of RAB14, thus promoting the migration and invasion of colorectal cancer cells 31 ; in renal cell carcinoma, DUXAP8 targets miR-126 and promotes cancer progression. 13 Based on the difference in the expression and role of DUXAP8 and miR-422a in HCC, we speculated that there was a regulatory relationship between them. We validated the binding relationship between DUXAP8 and miR-422a by dual-luciferase reporter gene assay.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, the role of lncRNA double homeobox A pseudogene 8 (DUXAP8) has been gradually studied in cancers. Studies show that DUXAP8 exerts a regulatory role in esophageal squamous cell carcinoma, renal cell carcinoma, gastric cancer, and other tumors . A recent study reports that in HCC, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with EZH2 .…”

Section: Introductionmentioning

confidence: 99%

“…Studies show that DUXAP8 exerts a regulatory role in esophageal squamous cell carcinoma, renal cell carcinoma, gastric cancer, and other tumors. [11][12][13] A recent study reports that in HCC, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with EZH2. 14 However, the function and mechanism of DUXAP8 in HCC needs further exploration.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Whereas decrease expression of CADM1-AS1 [28], NBAT-1 [29,30], lnc-ZNF180-2 [31], NONHSAT123350 [32], downregulate RNA in androgen independent cells (DRAIC) [33], and EPB41L4A-AS2 [34] were related to poor prognosis ( Table 1). The newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107bp RNA, was markedly upregulated in RCC [35]. Deciphering the molecular and biological mechanism(s) suggested that lncRNA DUXAP8 enhanced RCC progression through downregulating miR-126, which opens new prognostic approach for the treatment of RCC [35].…”

Section: Long Noncoding Rnas As Biomarker In Renal Cell Carcinomamentioning

confidence: 99%

Noncoding RNAs and Its Implication as Biomarkers in Renal Cell Carcinoma: A Systematic Analysis

Verma¹,

Gupta²

2019

ann urol oncol

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Renal cell carcinoma (RCC) is one of the most devastating disease with higher mortality rates. It comprises several subtypes exhibiting distinct histological features and clinical staging. Despite recent advancement in understanding the biology of RCC success in treatment rates remains dismal. This may be partly due to lack of specific biomarkers for early detection/prognosis and poor clinical outcome. Noncoding protein transcripts in the genome play important role in the initiation, evolution and progression of cancer. With the advancement in genomic analysis techniques, especially next-generation sequencing, a large number of new transcripts have been discovered, leading to better understanding of coding and noncoding RNAs. In the present review, we summarize recent advancement on renal cancer associated noncoding RNAs which includes long noncoding RNAs, microRNAs, and circular RNAs for their involvement in RCC along with their clinical implication as prognostic and diagnosis biomarkers.

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Joint action of miR‐126 and MAPK/PI3K inhibitors against metastatic melanoma

et al. 2019

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Emerging data support the rationale of combined therapies in advanced melanoma. Specifically, the combined use of drugs with different mechanisms of action can reduce the probability of selecting resistant clones. To identify agents active against melanoma cells, we screened a library of 349 anti‐cancer compounds, currently in clinical use or trials, and selected PIK ‐75, an inhibitor of the phosphatidylinositol 3‐kinase/protein kinase B ( PI 3K/ AKT ) pathway, as the ‘top active’ drug. PIK ‐75 was then used alone or in combination with vemurafenib, the first BRAF inhibitor approved for patients with melanoma harboring BRAF mutations. We identified a combined dose of PIK ‐75 and vemurafenib that inhibited both the PI 3K/ AKT and mitogen‐activated protein kinase pathways, thereby overcoming any compensatory activation. In view of the important tumor suppressor function induced by restoring expression of microRNA (miR)‐126 in metastatic melanoma cells, we examined whether miR‐126 has a synergistic role when included in a triple combination alongside PIK ‐75 and vemurafenib. We found that enforced expression of miR‐126 (which alone can reduce tumorigenicity) significantly increased PIK ‐75 activity when used as either a single agent or in combination with vemurafenib. Interestingly, PIK ‐75 proved to be effective against early passage cell lines derived from patients’ biopsies and on melanoma cell lines resistant to either vemurafenib or dabrafenib, thus suggesting that it potentially has the capability to overcome drug resistance. Finally, the synergistic role played by miR‐126 in combination with vemurafenib and/or PIK ‐75 was demonstrated in vivo in mouse xenograft models, in which tumor growth inhibition was associated with increased apoptosis. These results not only show the efficacy of PIK ‐75 and vemurafenib co‐treatment but also indicate that restoration of miR‐126 expression in advanced melanoma can enhance their antitumor activity, which may possibly allow dose reduction to decrease adverse events without reducing the therapeutic benefits.

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Long Non-Coding RNA DUXAP8 Enhances Renal Cell Carcinoma Progression via Downregulating miR-126

Cited by 50 publications

References 27 publications

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

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

Noncoding RNAs and Its Implication as Biomarkers in Renal Cell Carcinoma: A Systematic Analysis

Joint action of miR‐126 and MAPK/PI3K inhibitors against metastatic melanoma

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