The putative tumor suppressor microRNA-30a-5p modulates clear cell renal cell carcinoma aggressiveness through repression of ZEB2

Chen, Zhenhua; Zhang, Jiaxing; Zhang, Zhiling; Feng, Zhaoyong; Wei, Jinhuan; Lü, Jun; Fang, Yong; Liang, Yen Nan; Cen, Junjie; Pan, Yihui; Huang, Yong; Zhou, Fangjian; Chen, Wei; Luo, Junhang

doi:10.1038/cddis.2017.252

Cited by 55 publications

(64 citation statements)

References 44 publications

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“…In this study, we demonstrated that miR-30a-5p was repressed in ccRCC in vivo and in vitro . Consistent with our results, in a recent elegant study, Chen et al shows that miR-30a-5p expression is restricted and the reduced expression of mir-30a-5p promotes ccRCC prognosis [31]. Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene, which is associated with ccRCC [32, 33].…”

Section: Discussionsupporting

confidence: 79%

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MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

Wang

Cai

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is known to function as a tumor suppressor in several different cancers. However, the expression levels, biological function, and underlying mechanisms of miR-30a-5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78 (GRP78) is a common cancer biomarker and promotes the growth and survival of cancer cells. The expression of GRP78 has been reported to be modulated by miR-30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78 expression was investigated. Methods: MiR-30a-5p expression was analyzed using bioinformatic software on open microarray datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8 and cell count assays. Western blotting, immunohistochemistry, luciferase reporter assays, and flow cytometry were employed to investigate the mechanisms of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR-30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the GRP78 expression was inversely correlated with the expression of miR-30a-5p in vivo and in vitro. The functional studies of GRP78 overexpression or knockdown demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells, and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression. Conclusion: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down-regulating GRP78 expression and modulating the unfolded protein response (UPR) pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate target in ccRCC treatment.

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Section: Discussionsupporting

confidence: 79%

“…But why miR-30a-5p expression was decreased in ccRCC is still completely unclear. Chen et al demonstrates that the miR-30a-5p expression is regulated by long noncoding RNA (lncRNA) DLEU2 in ccRCC [31]. Previous study also demonstrates that miR-30a expression could be also regulated by the protein encoded by VHL [34].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

Wang

Cai

Liu

et al. 2017

Cell Physiol Biochem

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“…24 Importantly, DLEU2 could act as an endogenous sponge by directly binding to miR-30a in renal cell carcinoma. 21 Here, we confirmed the existence of an interaction between DLEU2 and miR-455 in PC cells.…”

Section: Discussionsupporting

confidence: 75%

“…Long noncoding RNA DLEU2 is downregulated in leukemia and laryngeal carcinoma . However, it was found to be elevated in renal cell carcinoma cells, and higher expression of DLEU2 was associated with a poor prognosis in patients with renal cell carcinoma . These previous results indicated that DLEU2 might have distinct functions in different tumors but did not provide enough information about the biological activity and mechanism by which DLEU2 regulates carcinogenesis and progression of human tumors (including PC).…”

Section: Discussionmentioning

confidence: 88%

“…20 However, it was found to be elevated in renal cell carcinoma cells, and higher expression of DLEU2 was associated with a poor prognosis in patients with renal cell carcinoma. 21 These previous results indicated that DLEU2 might have distinct functions in different tumors but did not provide enough information about the biological activity and mechanism by which DLEU2 regulates carcinogenesis and progression of human tumors (including PC). In this study, our findings showed that upregulation of DLEU2 was a frequent occurrence in PC tissues, and DLEU2 dramatically promoted the proliferation and invasion of PC cells in vitro.…”

Section: Discussionmentioning

confidence: 90%

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Silencing of DLEU2 suppresses pancreatic cancer cell proliferation and invasion by upregulating microRNA‐455

Gong

et al. 2019

Cancer Science

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Long noncoding RNA (lnc RNA ) DLEU 2 has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of DLEU 2 in pancreatic cancer ( PC ) progression are poorly understood. In this study, we found that the DLEU 2 level was substantially upregulated in PC tissues and PC cell lines, and significantly associated with poor clinical outcomes in PC patients. Overexpression of DLEU 2 significantly induced PC cell proliferation and invasion, whereas knockdown of DLEU 2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation assay revealed that DLEU 2 directly bond to microRNA‐455 (miR‐455) and functioned as an endogenous sponge for miR‐455, which could remarkably suppress cell growth and invasion. We also determined that SMAD 2 was a direct target of miR‐455, and the restoration of SMAD 2 rescued cell growth and invasion that were reduced by DLEU 2 knockdown or miR‐455 overexpression. In addition, low miR‐455 expression and high SMAD 2 expression was correlated with poor patient survival. These results indicate that DLEU 2 is an important promoter of PC development, and targeting the DLEU 2/miR‐455/ SMAD 2 pathway could be a promising therapeutic approach in the treatment of PC .

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LncRNA DLEU2 promotes tumour growth by sponging miR‐337‐3p in human osteosarcoma

Liu

et al. 2020

Cell Biochemistry & Function

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According to statistics, abnormal regulation of lncRNAs pivotally influences multiple malignant tumours. DLEU2, as one of these lncRNAs, is detected to be related to growth and development of tumours. The molecular mechanisms of DLEU2 in osteosarcoma, however, are still unknown. QRT-PCR was adopted to analyse the correlations of clinicopathological features and prognosis of osteosarcoma cases with DLEU2. The influences of DLEU2 on cell migration and viability were evaluated independently by experiments in vitro and in vivo. Bioinformatics analysis, RNA immunoprecipitation (RIP) assay, and dual luciferase reporter gene assay confirmed the specific binding of DLEU2 to miR-337-3p. Moreover, rescue experiments were carried out to further evaluate the regulatory association between miR-337-3p expression and DLEU2. In osteosarcoma tissues and cells, DLEU2 expression level was raised remarkably in comparison with that in para-carcinoma normal tissues, and DLEU2 high expression had associations with poor prognosis, tumour stages, and TS of osteosarcoma cases. Cell migration ability and viability were blocked by DLEU2 knockdown but enhanced by ectopic DLEU2 expression in vitro and in vivo. Additionally, DLEU2 was found to sponge miR-337-3p and trigger the stimulating effect in osteosarcoma cells, which would be suppressed by miR-337-3p mimics. Furthermore, a negative correlation existed between miR-337-3p expression and DLEU2 in osteosarcoma tissues. This study manifests that DLEU2 sponges miR-337-3p to accelerate tumour growth and is confirmed to be a factor for poor prognosis of osteosarcoma cases. Significance of the Study: LncRNA DLEU2 has been reported to be dysregulated in many tumours; however, the functions and underlying mechanism of DLEU2 in osteosarcoma pathogenesis are still unknown. This study is the first to demonstrate the roles of DLEU2 in osteosarcoma and revealed that DLEU2 may serve as a ceRNA to sponge miR-337-3p and then promote the progression of osteosarcoma, providing a potential therapeutic target for osteosarcoma.

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The putative tumor suppressor microRNA-30a-5p modulates clear cell renal cell carcinoma aggressiveness through repression of ZEB2

Cited by 55 publications

References 44 publications

MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

Silencing of DLEU2 suppresses pancreatic cancer cell proliferation and invasion by upregulating microRNA‐455

LncRNA DLEU2 promotes tumour growth by sponging miR‐337‐3p in human osteosarcoma

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