HOTAIR Facilitates Endocrine Resistance in Breast Cancer Through ESR1/miR-130b-3p Axis: Comprehensive Analysis of mRNA-miRNA-lncRNA Network

Zhang, Mingdi; Wu, Kangning; Zhang, Peng; Qiu, Yiran; Bai, Fang; Chen, Hongliang

doi:10.2147/ijgm.s320998

Cited by 11 publications

(11 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, some of these mutant TP53 -upregulated miRNAs have previously been shown to reduce ER expression in breast cancer models such as miR130b and miR301 (Supplementary Fig. 4e ) 55 , 58 , 59 .…”

Section: Resultsmentioning

confidence: 98%

Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer

Sikora

Richer

et al. 2022

npj Breast Cancer

View full text Add to dashboard Cite

Both TP53 and ESR1 mutations occur frequently in estrogen receptor positive (ER+) metastatic breast cancers (MBC) and their distinct roles in breast cancer tumorigenesis and progression are well appreciated. Recent clinical studies discovered mutual exclusivity between TP53 and ESR1 mutations in metastatic breast cancers; however, mechanisms underlying this intriguing clinical observation remain largely understudied and unknown. Here, we explored the interplay between TP53 and ESR1 mutations using publicly available clinical and experimental data sets. We first confirmed the robust mutational exclusivity using six independent cohorts with 1,056 ER+ MBC samples and found that the exclusivity broadly applies to all ER+ breast tumors regardless of their clinical and distinct mutational features. ESR1 mutant tumors do not exhibit differential p53 pathway activity, whereas we identified attenuated ER activity and expression in TP53 mutant tumors, driven by a p53-associated E2 response gene signature. Further, 81% of these p53-associated E2 response genes are either direct targets of wild-type (WT) p53-regulated transactivation or are mutant p53-associated microRNAs, representing bimodal mechanisms of ER suppression. Lastly, we analyzed the very rare cases with co-occurrences of TP53 and ESR1 mutations and found that their simultaneous presence was also associated with reduced ER activity. In addition, tumors with dual mutations showed higher levels of total and PD-L1 positive macrophages. In summary, our study utilized multiple publicly available sources to explore the mechanism underlying the mutual exclusivity between ESR1 and TP53 mutations, providing further insights and testable hypotheses of the molecular interplay between these two pivotal genes in ER+ MBC.

show abstract

Section: Resultsmentioning

confidence: 98%

Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer

Sikora

Richer

et al. 2022

npj Breast Cancer

View full text Add to dashboard Cite

show abstract

“…Apart from the p21 WAF1 /CIP1 and HOXA5 pathways, the most commonly acknowledged mechanism of HOTAIR is through the axis of microRNA (miR) and downstream signaling molecules. These axes include but are not limited to the following: HOTAIR/miR-222-3p/Cyclin Dependent Kinase 19 axis ( 46 ), HOTAIR/specificity protein 1/miR-199a axis ( 47 ), HOTAIR/miR-29b/phosphate and tension homology deleted on chromosome 10/PI3K axis ( 48 ), HOTAIR/miR-203/zinc finger E-box binding homeobox 1 axis ( 49 ), HOTAIR/estrogen receptor 1/miR-130b-3p axis ( 50 ), HOTAIR/miR-34a/Janus kinase 2/STAT3 axis ( 51 ), HOTAIR/miR-129-5p/ribosomal protein L14 axis ( 52 ), HOTAIR/miR-129-5p/frizzled class receptor 7 axis ( 53 ) and HOTAIR/miR-149-5p/doublecortin-like kinase 1 axis ( 54 ). Furthermore, HOTAIR also interacts with several classic signaling pathways, which are commonly involved in oncogenesis, such as CCL22 signaling ( 55 ), the Wnt/β-catenin signaling pathway ( 56 ), EZH2 and H3K27 methylation signaling ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

Association between long non‑coding RNA HOTAIR polymorphism and lung cancer risk: A systematic review and meta‑analysis

Feng²,

Li³

et al. 2022

Exp Ther Med

View full text Add to dashboard Cite

Single nucleotide polymorphism (SNP) of long noncoding RNA (lnc)RNA has been reported to be an important factor in cancer development. Recently, lncRNA homeobox transcript antisense intergenic RNA (HOTAIR) was indicated to induce tumorigenesis of several cancer types, but the association between the SNP of lncRNA HOTAIR and lung cancer susceptibility has remained undetermined. The present meta-analysis aimed to investigate the effect of HOTAIR polymorphism on susceptibility to lung cancer. The PubMed, Ovid Medline, Embase and Cochrane Library databases were thoroughly searched. Studies containing data on the incidence of lung cancer in patients with different HOTAIR SNPs were included. The Hardy-Weinberg equilibrium was analyzed to determine genotype distribution and allele frequencies. The odds ratio (OR) was pooled to evaluate the association of different SNPs with the susceptibility to lung cancer. A total of six studies comprising 1,715 patients with lung cancer and 2,745 healthy controls were finally included. A total of 4 SNPs (rs12826786, rs1899663, rs920778 and rs4759314) were reported. Analyses for all of these SNPs individually indicated that the lncRNA HOTAIR rs1899663 C>A polymorphism was a risk factor for lung cancer (dominant mode, AA+CA vs. CC: OR=0.816, 95% CI=0.707-0.942, P=0.005). The present study was the first meta-analysis investigating the association between lncRNA HOTAIR and lung cancer susceptibility. The results indicated that the lncRNA HOTAIR rs1899663 C>A polymorphism is a risk factor for lung cancer. LncRNA HOTAIR may be of value in lung cancer screening, particularly for populations with high-risk factors, as well as prognosis prediction. Future investigations are required to further clarify the intrinsic mechanism of the role of HOTAIR in the oncogenesis of lung cancer.

show abstract

“…A study on the clinical treatment of BC patients with E2 observed that HOTAIR can mediate endocrine therapy resistance via the hub gene ESR1 by targeting miR-130b-3p in BC patients [ 76 ]. It can also mediate trastuzumab resistance in BC cell lines by upregulating TGF-β, vimentin and Snail expression, downregulating E-cadherin levels, and increasing the methylation of PTEN gene (Fig.…”

Section: Hotair As a Driver Of Breast Cancermentioning

confidence: 99%

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer

et al. 2023

View full text Add to dashboard Cite

HOX transcript antisense intergenic RNA (HOTAIR) is an oncogenic non-coding RNA whose expression is strongly correlated with the tumor grade and prognosis of a variety of carcinomas including breast cancer (BC). HOTAIR regulates various target genes via sponging and epigenetic mechanisms and controls various oncogenic cellular and signaling mechanisms including metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by a variety of transcriptional and epigenetic mechanisms. In this review, we describe the regulatory mechanisms that govern HOTAIR expression during cancer development and explore how HOTAIR drives BC development, metastasis, and drug resistance. In the final section of this review, we focus on the role of HOTAIR in BC management, therapeutic treatment, and prognosis, highlighting its potential therapeutic applications.

show abstract

HOTAIR Facilitates Endocrine Resistance in Breast Cancer Through ESR1/miR-130b-3p Axis: Comprehensive Analysis of mRNA-miRNA-lncRNA Network

Cited by 11 publications

References 34 publications

Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer

Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer

Association between long non‑coding RNA HOTAIR polymorphism and lung cancer risk: A systematic review and meta‑analysis

HOTAIR: a potential metastatic, drug-resistant and prognostic regulator of breast cancer

Contact Info

Product

Resources

About