Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways

Jiang, Huijuan; Wang, Yiqing; Ai, Mei-Ling; Wang, Haowei; Duan, Zhijiao; Wang, Huanan; Zhao, Li; Yu, Jiang; Ding, Yan‐Qing; Wang, Shuang

doi:10.1038/cddis.2017.258

Cited by 81 publications

(78 citation statements)

References 48 publications

(55 reference statements)

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“…Among the remaining lncRNAs, CRNDE is one of the best studied oncogenic lncRNAs. In most cancer types, such as glioma, pancreatic cancer, cervical cancer, colorectal carcinoma, GC, clear cell renal cell carcinoma, and hepatocellular carcinoma, CRNDE can facilitate the proliferation, migration, invasion and metastasis of cancer cells, leading to a poor prognosis for patients with the above cancer types (Ding et al, 2018;Hu, Du, Zhang, & Huang, 2017;Jiang et al, 2017;Meng, Li, Li, & Ma, 2017;Tang, Zheng, & Zhang, 2018;G. Wang, Pan, Zhang, Wei, & Wang, 2017;Zheng et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression

Bai

Long

Liu

et al. 2019

Journal Cellular Physiology

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The aberrant expression of long noncoding RNAs (lncRNAs) has drawn increasing attention in the field of hepatocellular carcinoma (HCC) biology. In the present study, we obtained the expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in 371 HCC tissues and 50 normal tissues from The Cancer Genome Atlas (TCGA) and identified hepatocarcinogenesis‐specific differentially expressed genes (DEGs, log fold change ≥ 2, FDR < 0.01), including 753 lncRNAs, 97 miRNAs, and 1,535 mRNAs. Because the specific functions of lncRNAs are closely related to their intracellular localizations and because the cytoplasm is the main location for competitive endogenous RNA (ceRNA) action, we analyzed not only the interactions among these DEGs but also the distributions of lncRNAs (cytoplasmic, nuclear or both). Then, an HCC‐associated deregulated ceRNA network consisting of 37 lncRNAs, 10 miRNAs, and 26 mRNAs was constructed after excluding those lncRNAs located only in the nucleus. Survival analysis of this network demonstrated that 15 lncRNAs, 3 miRNAs, and 16 mRNAs were significantly correlated with the overall survival of HCC patients ( p < 0.01). Through multivariate Cox regression and lasso analysis, a risk score system based on 13 lncRNAs was constructed, which showed good discrimination and predictive ability for HCC patient survival time. This ceRNA network‐construction approach, based on lncRNA distribution, not only narrowed the scope of target lncRNAs but also provided specific candidate molecular biomarkers for evaluating the prognosis of HCC, which will help expand our understanding of the ceRNA mechanisms involved in the early development of HCC.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression

Bai

Long

Liu

et al. 2019

Journal Cellular Physiology

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“…Present study was initiated to examine interactions between long non-coding hsrω RNAs and Ras signaling cascade. Although, some studies have implicated oncogenic Ras to influence expression of several long non coding transcripts (Jiang et al, 2017;Jinesh et al, 2018;Kotake et al, 2016;Rotblat et al, 2011;Zhang et al, 2017b), regulation of Ras signaling cascade by lncRNAs is not yet known. While an earlier study from our lab showed that a ras mutant allele enhanced hsrω-null phenotype (Ray and Lakhotia, 1998), the present study shows that alterations in levels of hsrω transcripts exaggerate phenotypes that follow the sev-GAL4 driven expression of activated Ras in developing eye discs of Drosophila larvae.…”

Section: Discussionmentioning

confidence: 99%

Altered levels ofhsromegalncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation inDrosophila

Ray

Singh

Lakhotia

2017

Preprint

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To examine role of hsrω nuclear lncRNAs in Ras signaling cascade, we down-or up-regulated these transcripts in eye discs of Drosophila expressing sev-GAL4 driven activated ras V12 transgene. The sev-GAL4 driven Ras V12 transgene expression dependent late pupal lethality and extra R7 photoreceptors in ommatidia, were significantly enhanced when levels of hsrω lncRNA were down/up-regulated. This was associated with enhanced p-MAPK expression, reduced Yan levels, and greater association of RafRBDFLAG with Ras, indicating elevated Ras activation which was both cell autonomous and non-autonomous. RNAseq analysis revealed significant increase in expression of certain sno/sn/scaRNAs and some RNA processing genes in sevGAL4>Ras V12 which was further modulated when hsrωRNA levels were co-altered. Downregulation of hsrωRNAs elevated positive modulators of Ras signaling while their up-regulation reduced expression of negative modulators of Ras signaling, and thus both conditions have similar outcome. Further enhancement of activity of hyperactive Ras following changes in hsrω lncRNA levels in cell autonomous as well as non-autonomous manner emphasizes roles of lncRNAs in cell signaling during development and disease conditions associated with hyperactive Ras pathway mutants. SummaryOur findings highlight roles of hsrω lncRNA in conditionally modulating the important Ras signaling pathway and provide evidence for cell non-autonomous Ras signaling in Drosophila eye discs.

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“…The lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE), which was initially found to increase in colorectal cancer, was also overexpressed in various malignant diseases including HCC . Current evidences have suggested that CRNDE exert influence on the propagation and metastasis of malignant carcinoma . However, the expression profiles and precise biological functions of CRNDE in HCC remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…9 Current evidences have suggested that CRNDE exert influence on the propagation and metastasis of malignant carcinoma. 10 However, the expression profiles and precise biological functions of CRNDE in HCC remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR‐217/MAPK1 axis

Wang

Guo

et al. 2018

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC) is an invasive malignant tumour and the second major cause of cancer‐related deaths over the world. CRNDE and miR‐217 are non‐coding RNAs which play critical roles in cell growth, proliferation, migration. Mitogen‐activated protein kinase 1 (MAPK1) also participates in cancer cell process. Hence, this study aimed at investigating the effect of CRNDE on migration and invasion of HCC and figuring out the role of miR‐217 and MAPK1 in this process. The overexpression of CRNDE was demonstrated by a microarray‐based lncRNA profiling study. CRNDE expression in HCC was verified by qRT‐PCR. MTT assay and BrdU staining were applied to detect cell proliferation level. Transwell assay was utilized to examine cell migration and invasiveness abilities. Wound healing assay was performed for further exploration of cell migration capacity. MiR‐217 was predicted by bioinformatics. The dual luciferase reporter assay was performed to corroborate the targeting relationship between CRNDE, miR‐217 and MAPK1. MAPK1, the downstream target of miR‐217, was predicted using bioinformatics and was further confirmed by qRT‐PCR and Western blot. The interaction between CRNDE, miR‐217 and MAPK1 was studied by qRT‐PCR, Western blot, MTT, BrdU, transwell assay and wound healing assay. CRNDE was up‐regulated in HCC tissues and HCC cell lines. The high expression of CRNDE facilitated cell proliferation, migration and invasion, while the inhibited one affected on the contrary. MiR‐217, negatively correlated with CRNDE expression, was the target of CRNDE and was more lowly expressed in HCC. With the high expression of miR‐217, HCC cell proliferation, migration and invasion were suppressed. MAPK1, the possible target of miR‐217, was negatively correlated with miR‐217 but positively correlated with CRNDE and had the same effect in HCC formation process as CRNDE. Long non‐coding RNA CRNDE promotes the proliferation, migration and invasion of HCC cells through miR‐217/MAPK1 axis.

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Long noncoding RNA CRNDE stabilized by hnRNPUL2 accelerates cell proliferation and migration in colorectal carcinoma via activating Ras/MAPK signaling pathways

Cited by 81 publications

References 48 publications

Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression

Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression

Altered levels ofhsromegalncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation inDrosophila

Long non‐coding RNA CRNDE promotes the proliferation, migration and invasion of hepatocellular carcinoma cells through miR‐217/MAPK1 axis

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