Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

Mei, Jie; Hao, Lijun; Wang, Huiyu; Xu, Rui; Liu, Yan; Zhu, Yichao; Liu, Chaoying

doi:10.1111/cpr.12801

Cited by 49 publications

(46 citation statements)

References 165 publications

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“… 2 In the past few decades our understanding of the pathogenesis of BC has greatly improved but the prognosis is still not optimistic. 3 , 4 Therefore, a deeper understanding of the mechanisms behind BC progression is still needed.…”

Section: Introductionmentioning

confidence: 99%

LINC00665 Stimulates Breast Cancer Progression via Regulating miR-551b-5p

Sun²,

Yang³

et al. 2021

CMAR

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Introduction Long intergenic non-protein coding RNA 665 (LINC00665) has been revealed to contribute cancer progression in many cancer types including liver and gastric cancer. However, the roles of LINC00665 in breast cancer (BC) remain to be explored. Methods We explored LINC00665 expression in BC tissues and normal tissues at GEPIA. Then, its expression in BC cells (HCC-1937, MDA-MB-231, and MCF-7) and normal cells (MCF10A) was analyzed with qRT-PCR. In addition, the mechanisms of LINC00665 in BC were explored using bioinformatic analyses, luciferase activity reporter assay, RNA pull-down assay, and rescue experiments. Results We showed LINC00665 expression was significantly increased in both BC tissues and cells. The knockdown of LINC00625 significantly inhibits BC cell growth and promotes cell apoptosis in vitro, while the overexpression of LINC00625 has the opposite effects on BC progression. LINC00665 could affect BC progression via regulating miR-551b-5p. Discussion Taken together, our study showed that the LINC00665/miR-551b-5p axis was involved in the progression of BC.

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Section: Introductionmentioning

confidence: 99%

LINC00665 Stimulates Breast Cancer Progression via Regulating miR-551b-5p

Sun²,

Yang³

et al. 2021

CMAR

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“…Although HER2 mRNA was barely detected, circ-HER2 expression was identified in nearly 30% TNBC samples enrolled in this study and several established TNBC cell lines. Several reports addressed that circRNAs involved in proliferation or metastasis of TNBC; some circRNAs also had prognostic values [33]. However, current understanding of circRNAs in TNBC was limited to 'microRNA sponge', which absorbed micro RNAs and sequentially activated/inhibited downstream effectors [9,34].…”

Section: Discussionmentioning

confidence: 99%

Circular HER2 RNA positive triple negative breast cancer is sensitive to Pertuzumab

Yang

et al. 2020

Mol Cancer

113

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Background Triple negative breast cancer (TNBC) remains the most challenging breast cancer subtype so far. Specific therapeutic approaches have rarely achieved clinical improvements in treatment of TNBC patients and effective molecular biomarkers are largely unknown. Methods We used paired TNBC samples and high throughput RNA sequencing to identify differentially expressed circRNAs. Sucrose gradient polysome fractionation assay, antibody and Mass spectra were used to validate active circRNA translation. The novel protein function was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses and kinase activity assay. Results Circular HER2 RNA (circ-HER2) encoded a novel protein, HER2–103. Unexpectedly, while HER2 mRNA and protein were barely detected, circ-HER2/HER2–103 was expressed in ~ 30% TNBC clinical samples. Circ-HER2/HER2–103 positive TNBC patients harbored worse overall prognosis than circ-HER2/HER2–103 negative patients. Knockdown circ-HER2 inhibited TNBC cells proliferation, invasion and tumorigenesis in vitro and in vivo, suggesting the critical role of circ-HER2/HER2–103 in TNBC tumorigenicity. Mechanistically, HER2–103 promoted homo/hetero dimerization of epidermal growth factor receptor (EGFR)/HER3, sustained AKT phosphorylation and downstream malignant phenotypes. Furthermore, HER2–103 shared most of the same amino acid sequences as HER2 CR1 domain which could be antagonized by Pertuzumab, a clinical used HER2 antibody. Pertuzumab markedly attenuated in vivo tumorigenicity of circ-HER2/HER2–103 expressing TNBC cells but showed no effects in circ-HER2/HER2–103 negative TNBC cells. Conclusion Our results not only demonstrated that certain TNBCs were not truly ‘HER2 negative’ but also highlighted the clinical implications of Pertuzumab in circ-HER2/HER2–103 expressing TNBC patients.

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“…International Publisher of functional activities [6,7], and dysregulation of critical lncRNAs may contribute to the carcinogenesis and progression of EnCa [8,9]. Moreover, lncRNAs have been identified as crucial nodes in regulating tumor immunity in multiple cancers [10,11].…”

Section: Ivyspringmentioning

confidence: 99%

Development of a novel immune-related lncRNA signature as a prognostic classifier for endometrial carcinoma

Liu¹,

Mei²,

Wang³

et al. 2021

Int. J. Biol. Sci.

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Endometrial carcinoma (EnCa) is one of the deadliest gynecological malignancies. The purpose of the current study was to develop an immune-related lncRNA prognostic signature for EnCa. In the current research, a series of systematic bioinformatics analyses were conducted to develop a novel immune-related lncRNA prognostic signature to predict disease-free survival (DFS) and response to immunotherapy and chemotherapy in EnCa. Based on the newly developed signature, immune status and mutational loading between high-and low-risk groups were also compared. A novel 13-lncRNA signature associated with DFS of EnCa patients was ultimately developed using systematic bioinformatics analyses. The prognostic signature allowed us to distinguish samples with different risks with relatively high accuracy. In addition, univariate and multivariate Cox regression analyses confirmed that the signature was an independent factor for predicting DFS in EnCa. Moreover, a predictive nomogram combined with the risk signature and clinical stage was constructed to accurately predict 1-, 2-, 3-, and 5-year DFS of EnCa patients. Additionally, EnCa patients with different levels of risk had markedly different immune statuses and mutational loadings. Our findings indicate that the immune-related 13-lncRNA signature is a promising classifier for prognosis and response to immunotherapy and chemotherapy for EnCa.

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Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

Cited by 49 publications

References 165 publications

LINC00665 Stimulates Breast Cancer Progression via Regulating miR-551b-5p

LINC00665 Stimulates Breast Cancer Progression via Regulating miR-551b-5p

Circular HER2 RNA positive triple negative breast cancer is sensitive to Pertuzumab

Development of a novel immune-related lncRNA signature as a prognostic classifier for endometrial carcinoma

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