A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth

Li, Qiang; Wang, Xiao; Zhou, Liheng; Jiang, Mingyun; Zhong, Guansheng; Xu, Shuguang; Zhang, Minjun; Zhang, Yigan; Liang, Xiaodong; Zhang, Lei; Tang, Jianming; Zhang, Haibo

doi:10.3389/fonc.2021.619915

Cited by 14 publications

(15 citation statements)

References 32 publications

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“…The previous studies have uncovered that LINC00460 is a strong risk marker of BC [ 48 ] and can promote breast cancer progression by sponging miR-489-5p [ 49 ]. Similarly, CYTOR (also known as LINC00152) can increase cell proliferation, migration, and invasion of BC and is related to the bad outcome of BC patients [ 50 , 51 ]. Furthermore, in accordance with our findings, some other studies mainly based on the bioinformatics analysis have also reported that LINC02408 [ 52 ] and YTHDF3-AS1 [ 53 ] are connected with the poor prognosis of BC patients, but USP30-AS1 [ 54 ], U73166.1 [ 55 ], and LINC01016 [ 30 ] can be taken as the protective factors of prognosis.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

Xie

Zhou

et al. 2022

Genes

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Long non-coding RNAs (lncRNAs) have been well known for their multiple functions in the tumorigenesis, development, and prognosis of breast cancer (BC). Mechanistically, their production, function, or stability can be regulated by RNA binding proteins (RBPs), which were also involved in the carcinogenesis and progression of BC. However, the roles and clinical implications of RBP-related lncRNAs in BC remain largely unknown. Therefore, we herein aim to construct a prognostic signature with RBP-relevant lncRNAs for the prognostic evaluation of BC patients. Firstly, based on the RNA sequencing data of female BC patients from The Cancer Genome Atlas (TCGA) database, we screened out 377 differentially expressed lncRNAs related to RBPs. The univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were then performed to establish a prognostic signature composed of 12-RBP-related lncRNAs. Furthermore, we divided the BC patients into high- and low-risk groups by the prognostic signature and found the overall survival (OS) of patients in the high-risk group was significantly shorter than that of the low-risk group. Moreover, the 12-lncRNA signature exhibited independence in evaluating the prognosis of BC patients. Additionally, a functional enrichment analysis revealed that the prognostic signature was associated with some cancer-relevant pathways, including cell cycle and immunity. In summary, our 12-lncRNA signature may provide a theoretical reference for the prognostic evaluation or clinical treatment of BC patients.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

Xie

Zhou

et al. 2022

Genes

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“…CYTOR was elevated in breast tumors and in plasma from BC patients compared to normal controls [ 99 ]. Higher CYTOR was associated with reduced OS in a study of 70 breast tumors [ 100 ]. This study identified an interaction between CYTOR and KLF5 in MDA-MB-231 and MCF-7 cells that stabilized KLF5 (Kruppel-like factor 5) protein and enhanced tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

“…This study identified an interaction between CYTOR and KLF5 in MDA-MB-231 and MCF-7 cells that stabilized KLF5 (Kruppel-like factor 5) protein and enhanced tumorigenesis. The authors also demonstrated that KLF5 binds the CYTOR promoter and increases CYTOR transcription [ 100 ]. CYTOR (LINC00152) was identified in network 3 ( Supplementary Table S2 ) with DLEU7-AS1, GAS5, SOX2OT, and TUG1 ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

Muluhngwi

Klinge

2021

Cancers

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Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We examined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in endocrine-resistant breast cancer.

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“…For example, in breast tumors, LINC000906, with predicted activity as an miRNA sponge in breast tumors and correlated with overall survival in breast cancer patients, was associated with 115 pcGenes, the largest association with MS4A5, a gene whose hypomethylation is shown to be prognostic for multiple cancer types 66,67 . LINC00115, a known promoter of breast and ovarian cancer metastasis and progression [68][69][70] , is another example of an ncRNA associated with multiple different pcGenes, many of which are interferon-related genes (IFNA17 and IFNW1), related to immune system cytotoxicity (RAC2 and DDB2), or coding for secretory proteins (PRH1 and…”

Section: Gene-based Distal-eqtl Mappingmentioning

confidence: 99%

Distal gene regulation mediated by non-coding RNAs contributes to germline risk for breast and prostate cancer

Cole

Lee

Schwarz

et al. 2022

Preprint

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Genome-wide association studies (GWAS) have identified numerous genetic loci associated with breast and prostate cancer risk, suggesting that germline genetic dysregulation influences tumorigenesis. However, the biological function underlying many genetic associations is not well-understood. Previous efforts to annotate loci focused on protein-coding genes (pcGenes) largely ignore non-coding RNAs (ncRNAs) which account for most transcriptional output in human cells and can regulate transcription of both pcGenes and other ncRNAs. Though the biological roles of most ncRNAs are not well-defined, many ncRNAs are involved in cancer development. Here, we explore one regulatory hypothesis: ncRNAs as trans-acting mediators of gene expression regulation in non-cancerous and tumor breast and prostate tissue. Using germline genetics as a causal anchor, we categorize distal (>1 Megabase) expression quantitative trait loci (eQTLs) of pcGenes significantly mediated by local-eQTLs of ncRNAs (within 1 Megabase). We find over 300 mediating ncRNAs and show the linked pcGenes are enriched for immunoregulatory and cellular organization pathways. By integrating eQTL and cancer GWAS results through colocalization and genetically-regulated expression analyses, we detect overlapping signals in nine known breast cancer loci and one known prostate cancer locus, and multiple novel genetic associations. Our results suggest a strong transcriptional impact of ncRNAs in breast and prostate tissue with implications for cancer etiology. More broadly, our framework can be systematically applied to functional genomic features to characterize genetic variants distally-regulating transcription through trans-mechanisms.

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A Positive Feedback Loop of Long Noncoding RNA LINC00152 and KLF5 Facilitates Breast Cancer Growth

Cited by 14 publications

References 32 publications

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

Integrated Analysis of RNA Binding Protein-Related lncRNA Prognostic Signature for Breast Cancer Patients

Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

Distal gene regulation mediated by non-coding RNAs contributes to germline risk for breast and prostate cancer

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