Identification of lncRNA NEAT1/miR‐21/RRM2 axis as a novel biomarker in breast cancer

Quan, Dongling; Chen, Kai; Zhang, Jingru; Guan, Yiqing; Yang, Danni; Wu, Haiwei; Wu, Shaoyu; Lv, Lin

doi:10.1002/jcp.29225

Cited by 35 publications

(37 citation statements)

References 25 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NEAT1 suppresses miR-124 and NF-κB pathway. Similarly, several lncRNA-miRNA interactions were confirmed by experimental testing, including MALAT1-miR-21 (Huang et al, 2020), MALAT1-miR-30 (Yi et al, 2019), NEAT1-miR-21 (Quan et al, 2020), and NEAT1-let-7a (Liu et al, 2018). These results provide experimental support for our analysis on the cooperative function of lncRNAs in DN development and progression.…”

Section: Discussionsupporting

confidence: 78%

Identification of Cooperative Gene Regulation Among Transcription Factors, LncRNAs, and MicroRNAs in Diabetic Nephropathy Progression

Chen

Wang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

The pathogenesis of diabetic nephropathy (DN) is accompanied by alterations in biological function and signaling pathways regulated through complex molecular mechanisms. A number of regulatory factors, including transcription factors (TFs) and non-coding RNAs (ncRNAs, including lncRNAs and miRNAs), have been implicated in DN; however, it is unclear how the interactions among these regulatory factors contribute to the development of DN pathogenesis. In this study, we developed a network-based analysis to decipher interplays between TFs and ncRNAs regulating progression of DN by combining omics data with regulatory factor-target information. To accomplish this, we identified differential expression programs of mRNAs and miRNAs during early DN (EDN) and established DN. We then uncovered putative interactive connections among miRNA-mRNA, lncRNA-miRNA, and lncRNA-mRNA implicated in transcriptional control. This led to the identification of two lncRNAs (MALAT1 and NEAT1) and the three TFs (NF-κB, NFE2L2, and PPARG) that likely cooperate with a set of miRNAs to modulate EDN and DN target genes. The results highlight how crosstalk among TFs, lncRNAs, and miRNAs regulate the expression of genes both transcriptionally and post-transcriptionally, and our findings provide new insights into the molecular basis and pathogenesis of progressive DN.

show abstract

Section: Discussionsupporting

confidence: 78%

Identification of Cooperative Gene Regulation Among Transcription Factors, LncRNAs, and MicroRNAs in Diabetic Nephropathy Progression

Chen

Wang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…NEAT1 functions as a competing endogenous RNA (ceRNA) in multiple tumor cells ( 19 ). Thus, we speculated that NEAT1 sponges miRNAs in HFLS-RA cells.…”

Section: Resultsmentioning

confidence: 99%

LncRNA NEAT1 Targets Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via the miR-410-3p/YY1 Axis

et al. 2020

View full text Add to dashboard Cite

LncRNA NEAT1 functions as an oncogene in multiple human cancers. However, its expression and role in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) remain unclear. Thus, we investigated the expression of NEAT1 in synovial tissues and FLSs in RA, to determine its role in the development of RA. Quantitative real-time polymerase chain reaction was used to measure the expression of NEAT1. FLS proliferation was evaluated using cell proliferation assays. Flow cytometry was used to analyze cell cycle progression and apoptosis in FLSs. Binding between NEAT1 and miR-410-3p was demonstrated by dual-luciferase assays. We found that NEAT1 was upregulated in synovial tissues and FLSs in RA. Upregulation of NEAT1 promoted cell proliferation, induced S-to G2/M phase transition, and suppressed apoptosis in RA FLSs. NEAT1 directly bound to and negatively modulated miR-410-3p expression, while positively regulating YinYang 1(YY1; a miR-410-3p target). Inhibiting miR-410-3p and upregulating YY1 partially restored the inhibitory role in cell viability induced by the depletion of NEAT1 in RA FLSs. Besides pro-proliferative and anti-apoptotic roles, upregulation of NEAT1 promoted migration, invasion, and inflammatory cytokines secretion in RA FLSs. Taken together, our results suggest that the NEAT1 may serve as a novel diagnostic and therapeutic target for patients with RA.

show abstract

“…Ribonucleotide reductase subunit M2 (RRM2) is rate-limiting enzyme for DNA synthesis and repair, which has essential roles in cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis (Chen et al 2019). RRM2 was found to be upregulated in various breast cancer cells, especially in triple negative breast cancer (Quan et al 2019). Worse overall survival was observed in breast cancer patients with increased RRM2, which had an enhancing effect on relapsing metastases.…”

Section: Discussionmentioning

confidence: 99%

Conditional knockdown of integrin beta-3 reveals its involvement in osteolytic and soft tissue lesions of breast cancer skeletal metastasis

Kovacheva

Zepp

Berger

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Integrin β3 (ITGB3) is probably related to skeletal metastasis, which is the most frequent complication in breast cancer progression. We aimed to define its role and suitability as target for anti-metastatic therapy. We generated two MDA-MB-231 cell clones with conditional miRNA-mediated ITGB3 knockdown for analyzing the resulting effects in vitro regarding mRNA expression, proliferation and migration, as well the impact on skeletal metastasis in a nude rat model. Furthermore, ITGB3 levels were analyzed in exosomes from plasma of rats with skeletal metastases, and from MDA-MB-231 cells incubated with these vesicles, as well as from exosomes secreted by cells with conditional ITGB3 knockdown. This inhibition of ITGB3 expression decreased cellular proliferation and more distinctly inhibited cellular migration. Reduction and even complete remissions of respective soft tissue and osteolytic lesions were detected after ITGB3 knockdown in vivo. Furthermore, ITGB3 levels were increased in exosomes isolated from plasma of rats harboring MDA-MB-231 lesions as well as in respective cells incubated with these vesicles in vitro. ITGB3 was distinctly decreased in exosomes from cells with ITGB3 knockdown. The observed in vitro and in vivo anti-ITGB3 effects can be explained by downregulation of specific genes, which have roles in angiogenesis (NPTN, RRM2), tumor growth (NPTN), energy metabolism (ISCA1), cytokinesis (SEPT11), migration (RRM2, STX6), cell proliferation, invasiveness, senescence, tumorigenesis (RRM2) and vesicle trafficking (SEPT11, STX6). ITGB3 has a role in breast cancer skeletal metastasis via gene expression modulation, as mirrored for ITGB3 in exosomes, thus it could serve as target for anti-metastatic therapy.

show abstract

Identification of lncRNA NEAT1/miR‐21/RRM2 axis as a novel biomarker in breast cancer

Cited by 35 publications

References 25 publications

Identification of Cooperative Gene Regulation Among Transcription Factors, LncRNAs, and MicroRNAs in Diabetic Nephropathy Progression

Identification of Cooperative Gene Regulation Among Transcription Factors, LncRNAs, and MicroRNAs in Diabetic Nephropathy Progression

LncRNA NEAT1 Targets Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via the miR-410-3p/YY1 Axis

Conditional knockdown of integrin beta-3 reveals its involvement in osteolytic and soft tissue lesions of breast cancer skeletal metastasis

Contact Info

Product

Resources

About