Rap2B promotes proliferation, migration and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway

Di, Jiehui; Huang, Hui; Qu, Debao; Tang, Juangjuan; Cao, Wenjia; Qian, Cheng; Yang, Jing; Bai, Jing; Zhang, Yanping; Zheng, Junnian

doi:10.1038/srep12363

Cited by 77 publications

(71 citation statements)

References 45 publications

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“…Subsequently, the plasmid of si-MDM2 was transfected into MP65 cells to silence MDM2 expression, and the transfection efficiency was shown in Figure 6f. Results in (Di et al, 2015). Recent study shows that activation of the ERK1/2 pathway is a common event in uveal melanoma .…”

Section: Ras-erk1/2 Pathway Degrades Tip60 By the Mediation Of Mdm2mentioning

confidence: 98%

Retracted: Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac

Sun

et al. 2019

Journal Cellular Physiology

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Ras–extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling has been proposed as the crucial regulators in the development of various cancers. Histone acetylation at H3 lysine 14 (H3K14ac) is closely associated with gene expression and DNA damage. However, whether H3K14ac participates in mediating Ras–ERK1/2‐induced cell proliferation and migration in uveal melanoma cells remains unknown. The purpose of this study is to investigate the effect of H3K14ac on Ras–ERK1/2 affected uveal melanoma cell phenotypes. MP65 cells were transfected with Ras WT and Ras G12V/T35S, the unloaded plasmid of pEGFP‐N1 served as a negative control. Protein levels of phosphorylated ERK1/2 Thr202 and H3K14ac were assessed by western blot assay. Cell viability, number of colonies, migration, and the downstream genes of ERK1/2 were analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, soft‐agar colony formation, transwell, and chromatin immunoprecipitation assays. HA‐tag vectors of CLR3 and TIP60 and the small interfering RNAs that specific for CLR3 and MDM2 were transfected into MP65 cells to uncover the effects of CLR3, TIP60, and MDM2 on Ras–ERK1/2 mediated H3K14ac expression and MP65 cell phenotypes. We found that, Ras–ERK1/2 decreased H3K14ac expression in MP65 cells, and H3K14ac significantly suppressed Ras–ERK1/2‐induced cell viability, colony formation, and migration in MP65 cells. Moreover, the transcription of CYR61, IGFBP3, WNT16B, NT5E, GDF15, and CARD16 was regulated by H3K14ac. Additionally, CLR3 silence recovered H3K14ac expression and reversed the effect of Ras–ERK1/2 on MP65 cell proliferation, migration and the mRNAs of ERK1/2 downstream genes. Besides, Ras–ERK1/2 decreased H3K14ac expression by MDM2‐mediated TIP60 degradation. In conclusion, Ras–ERK1/2 promoted uveal melanoma cells growth and migration by downregulating H3K14ac via MDM2‐mediated TIP60 degradation.

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Section: Ras-erk1/2 Pathway Degrades Tip60 By the Mediation Of Mdm2mentioning

confidence: 98%

Retracted: Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac

Sun

et al. 2019

Journal Cellular Physiology

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“…Among these pathways, such as the 'PI3K-Akt signaling pathway', is involved in the carcinogenesis of gastric adenocarcinoma metastases (21), the 'Wnt signaling pathway' has been investigated as a cause of adenocarcinoma invasion (22) and the gene category 'Pathways in cancer' is involved in the development of GC. In addition, some pathways such as 'Small cell lung cancer, Cell adhesion molecules (CAMs), Proteoglycans in cancer and Transcriptional regulation in cancer' were also reported as cancers related pathways (23,24) (Fig. 5).…”

Section: Go and Pathway Analysis Of Differentially Expressed Genesmentioning

confidence: 99%

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

Liang

Yao

et al. 2016

International Journal of Oncology

111

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Abstract. Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05).The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis. IntroductionNoncoding RNAs (ncRNAs) are transcripts that have no ability of coding proteins, which widely exit in high eukaryotics. According to their characteristics, ncRNAs can be divided into several subtypes including transfer RNA, small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), microRNA (miRNA) and long non-coding RNA (lncRNA). The amount of the ncRNAs transcripts is >98% of the whole genome transcripts and have been suggested to represent transcriptional noise (1). However, more and more evidence indicates that transcriptional output of genome is far more complex than predicted, and suggests new paradigms of ncRNA regulation (2).Recent studies suggest that the ncRNAs may play important biological roles in transcriptional regulation, cellular development, formation of chromosome and RNA modification (3). Based on the transcript size, ncRNAs are grouped into small ncRNAs (<200 bp) and long ncRNAs (>200 bp, up to 100 kb). lncRNA is the functional end-product, and the level of lncRNA expression correlates directly with the level of the active molecule. Thus, ...

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“…Previous work demonstrated that Rap-2b is a target of p53 and it counteracts p53-mediated apoptosis [72]. Moreover, Rap-2b can affect cytoskeleton reorganisation and cell migration [73,74]. Given the role of Rap-2b in transformation, it may be that upregulation of this gene contributes to AAI-induced carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

The Impact of p53 on Aristolochic Acid I-Induced Gene Expression In Vivo

Sborchia

Keun

Phillips

et al. 2019

IJMS

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Exposure to aristolochic acid (AA) is linked to kidney disease and urothelial cancer in humans. The major carcinogenic component of the AA plant extract is aristolochic acid I (AAI). The tumour suppressor p53 is frequently mutated in AA-induced tumours. We previously showed that p53 protects from AAI-induced renal proximal tubular injury, but the underlying mechanism(s) involved remain to be further explored. In the present study, we investigated the impact of p53 on AAI-induced gene expression by treating Trp53(+/+), Trp53(+/-), and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for six days. The Clariom™ S Assay microarray was used to elucidate gene expression profiles in mouse kidneys after AAI treatment. Analyses in Qlucore Omics Explorer showed that gene expression in AAI-exposed kidneys is treatment-dependent. However, gene expression profiles did not segregate in a clear-cut manner according to Trp53 genotype, hence further investigations were performed by pathway analysis with MetaCore™. Several pathways were significantly altered to varying degrees for AAI-exposed kidneys. Apoptotic pathways were modulated in Trp53(+/+) kidneys; whereas oncogenic and pro-survival pathways were significantly altered for Trp53(+/-) and Trp53(-/-) kidneys, respectively. Alterations of biological processes by AAI in mouse kidneys could explain the mechanisms by which p53 protects from or p53 loss drives AAI-induced renal injury in vivo.

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Rap2B promotes proliferation, migration and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway

Cited by 77 publications

References 45 publications

Retracted: Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac

Retracted: Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

The Impact of p53 on Aristolochic Acid I-Induced Gene Expression In Vivo

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