Long Non-Coding RNA: Dual Effects on Breast Cancer Metastasis and Clinical Applications

Huang, Qi-Yuan; Li, Guofeng; Qian, Xiaoqin; Tang, Libo; Xiong, Likuan

doi:10.3390/cancers11111802

Cited by 50 publications

(46 citation statements)

References 203 publications

(222 reference statements)

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“…Currently, a rising number of studies have managed to investigate the association between lncRNAs and breast cancer. LncRNAs have dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of breast cancer cells [27]. In addition, lncRNAs have critical regulatory effects in the stemness and angiogenesis of breast cancer [28].…”

Section: Discussionmentioning

confidence: 99%

LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway

Yang

et al. 2020

Cancer Cell Int

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Background: Long non-coding RNA H19 (lncRNA H19) has been implicated in tumorigenesis and metastasis of breast cancer through regulating epithelial to mesenchymal transition (EMT); however, the underlying mechanisms remain elusive. Methods: LncRNA H19 and TNFAIP8 were identified by qRT-PCR and western blotting. CCK-8 assay, clone formation assay, transwell assay, and flow cytometry assay were performed to determine cell proliferation, migration, invasion and cell cycle of breast cancer respectively. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the protein expression levels of p53, TNFAIP8, and marker proteins of EMT cascades in vivo. Dual luciferase reporter assay and RNA pull down assay were conducted to evaluate the interactions of lncRNA H19, p53 and TNFAIP8. Results: The expression of lncRNA H19 and TNFAIP8 was up-regulated in breast cancer tissues and cell lines, especially in triple-negative breast cancer (TNBC). Functionally, knockdown of lncRNA H19 or TNFAIP8 coused the capacities of cell proliferation, migration, and invasion were suppressed, and cell cycle arrest was induced, as well as that the EMT markers were expressed abnormal. Mechanistically, lncRNA H19 antagonized p53 and increased expression of its target gene TNFAIP8 to promote EMT process. Furthermore, silencing of lncRNA H19 or TNFAIP8 also could inhibit tumorigenesis and lymph node metastases of MDA-MB-231 cells in xenograft nude mouse models. Conclusions: Our findings provide insight into a novel mechanism of lncRNA H19 in tumorigenesis and metastases of breast cancer and demonstrate H19/p53/TNFAIP8 axis as a promising therapeutic target for breast cancer, especially for TNBC.

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Section: Discussionmentioning

confidence: 99%

LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway

Yang

et al. 2020

Cancer Cell Int

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“…Thus, there is urgent need to exploit the novel and effective biomarkers for early diagnosis, treatment option, and survival evaluation to improve the prognosis for BRCA. In the past decades, more and more studies provided evidences to support that lncRNAs might play key roles in tumorigenesis, progression and invasion in breast cancer [15,35]. According to previous researches, lncRNAs were reported as crucial regulators in regulating cancer immunity [12].…”

Section: Discussionmentioning

confidence: 99%

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Xu¹,

Wang²,

Huang³

2020

Preprint

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Background: There have numerous evidences to support that long non-coding RNAs (lncRNAs) may be crucial parts in cancer immunity. We aimed to establish a novel and robust immune-associated lncRNAs signature to improve prognostic precision in patients with breast cancer(BRCA).Methods: BRCA cases were obtained from the The Cancer Genome Atlas (TCGA) database. Immune‐related lncRNAs presenting significant association with prognosis were screened through stepwise univariate Cox regression and LASSO algorithm, and multivariate Cox regression. Kaplan-Meier analysis, ROC analyses, and proportional hazards model further conducted. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) was applied for functional annotation. The correlation between immune checkpoint inhibitors and this signature was employed. Results: 13 immune-related lncRNAs were systematically identified to establish immune-related lncRNAs predictive prognosis signature. The risk model we built showed significant correlation with BRCA patients’ prognosis. The value of ROC for this lncRNAs model was up to 0.821. This immune‐related lncRNAs signature can serve as an independent prognostic biomolecular factor. Our lncRNAs signature involved in chondrocyte development, endoderm development and so forth. This lncRNAs risk model was associated with tumor immune infiltration (i.e., B cells, Dendritic, Neutrophils, CD8 T cells and CD4 T cells, etc.,) and immune checkpoint blockade (ICB) therapy key molecules (i.e., PDCD1).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with BRCA and may have the capability to predict the clinical outcome of ICB treatment, which could provide guidance for immunological decision in patients with BRCA.

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“…Like miRNAs, there has been a multitude of studies linking the dysregulation of lncRNAs to cancer. Thus, it was repeatedly shown that abnormal expression of numerous lncRNAs among which, for example, MALAT1, HOTAIR, and DANCR, contributes to BC aggressiveness, metastasis formation, and hence BC patients' prognosis outcome 3 . Therefore, owing to their clinical implications and networks of crosstalk, both miRNAs and lncRNAs are explored as therapeutic and diagnostic options in cancer and subjected to extensive research.…”

Section: Non-coding Rnas In Cancermentioning

confidence: 99%

Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer

et al. 2021

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The epithelial–mesenchymal transition (EMT) plays a pivotal role in the differentiation of vertebrates and is critically important in tumorigenesis. Using this evolutionarily conserved mechanism, cancer cells become drug-resistant and acquire the ability to escape the cytotoxic effect of anti-cancer drugs. In addition, these cells gain invasive features and increased mobility thereby promoting metastases. In this respect, the process of EMT is critical for dissemination of solid tumors including breast cancer. It has been shown that miRNAs are instrumental for the regulation of EMT, where they play both positive and negative roles often as a part of a feed-back loop. Recent studies have highlighted a novel association of p53 and EMT where the mutation status of p53 is critically important for the outcome of this process. Interestingly, p53 has been shown to mediate its effects via the miRNA-dependent mechanism that targets master-regulators of EMT, such as Zeb1/2, Snail, Slug, and Twist1. This regulation often involves interactions of miRNAs with lncRNAs. In this review, we present a detailed overview of miRNA/lncRNA-dependent mechanisms that control interplay between p53 and master-regulators of EMT and their importance for breast cancer.

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Long Non-Coding RNA: Dual Effects on Breast Cancer Metastasis and Clinical Applications

Cited by 50 publications

References 203 publications

LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway

LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway

Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Breast Cancer

Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer

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