scholarly journals Splicing dysregulation as a driver of breast cancer

2018 ◽  
Vol 25 (9) ◽  
pp. R467-R478 ◽  
Author(s):  
Abigail Read ◽  
Rachael Natrajan
Keyword(s):  
Breast Cancer ◽  
High Throughput Sequencing ◽  
Predictive Biomarkers ◽  
Therapy Resistance ◽  
Complete Understanding ◽  
Molecular Abnormalities ◽  
Sequencing Technologies ◽  
Large Repertoire ◽  
Positive Breast Cancer

Breast cancer is known to be a heterogeneous disease driven by a large repertoire of molecular abnormalities, which contribute to its diverse clinical behaviour. Despite the success of targeted therapy approaches for breast cancer patient management, there is still a lack of the molecular understanding of aggressive forms of the disease and clinical management of these patients remains difficult. The advent of high-throughput sequencing technologies has paved the way for a more complete understanding of the molecular make-up of the breast cancer genome. As such, it is becoming apparent that disruption of canonical splicing within breast cancer governs its clinical progression. In this review, we discuss the role of dysregulation of spliceosomal component genes and associated factors in the progression of breast cancer, their role in therapy resistance and the use of quantitative isoform expression as potential prognostic and predictive biomarkers with a particular focus on oestrogen receptor-positive breast cancer.

scholarly journals Decoding the Oncogenic Signals from the Long Non-Coding RNAs

Onco ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 176-206
Author(s):  
Revathy Nadhan ◽  
Danny N. Dhanasekaran
Keyword(s):  
High Throughput Sequencing ◽  
Critical Role ◽  
Therapy Resistance ◽  
Signaling Cascades ◽  
Clear Understanding ◽  
Sequencing Technologies ◽  
Cancer Cell Survival ◽  
Non Coding Rnas ◽  
Insight Into

Cancer is one of the leading causes of death worldwide. Multifactorial etiology of cancer and tumor heterogeneity are the two most acute challenges in existing diagnostic and therapeutic strategies for cancer. An effective precision cancer medicine strategy to overcome these challenges requires a clear understanding of the transcriptomic landscape of cancer cells. Recent innovative breakthroughs in high-throughput sequencing technologies have identified the oncogenic or tumor-suppressor role of several long non-coding RNAs (lncRNAs). LncRNAs have been characterized as regulating various signaling cascades which are involved in the pathobiology of cancer. They modulate cancer cell survival, proliferation, metabolism, invasive metastasis, stemness, and therapy-resistance through their interactions with specific sets of proteins, miRNAs and other non-coding RNAs, mRNAs, or DNAs in cells. By virtue of their ability to regulate multiple sets of genes and their cognate signaling pathways, lncRNAs are emerging as potential candidates for diagnostic, prognostic, and therapeutic targets. This review is focused on providing insight into the mechanisms by which different lncRNAs play a critical role in cancer growth, and their potential role in cancer diagnosis, prognosis, and therapy.

scholarly journals Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer

2018 ◽  
Vol 19 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Peng Liu ◽  
Hailin Tang ◽  
Jiali Wu ◽  
Xingsheng Qiu ◽  
Yanan Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Mouse Xenograft ◽  
Her2 Positive Breast Cancer ◽  
Mouse Xenograft Model ◽  
Positive Breast Cancer

Background: Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer, remains largely unknown. Objective: To investigate the effect of linc01638 on tumorigenesis in HER2-positive breast cancer. </P><P> Methods: We first used qRT-PCR to detect linc01638 expression in HER2-positive breast cancer cells and tissues. Then we analyzed the effects of linc01638 expression in HER2-positive breast cancer cells through cell apoptosis assay, cell proliferation assay, colony formation assay, and cell invasion assay. We conducted mouse xenograft model to further confirm the role of linc01638 in HER2-positive breast cancer. Moreover, we used Western blot and IHC analysis to access the effect of linc01638 on DNMTs, BRCA1 and PTEN expressions in transplanted tumors. Results: Linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo. Furthermore, inhibition of linc01638 by shRNA attenuated expression of DNMT1, DNMT3a, and DNMT3b, and promoted expression of BRCA1 and PTEN in HER2-positive breast cancer cells and mouse xenograft models. Linc01638 might be a promising biomarker and therapeutic target for treatment of HER2-positive breast cancer.

scholarly journals The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

2015 ◽  
Vol 290 (14) ◽  
pp. 8722-8733 ◽  
Author(s):  
Raju R. Rayavarapu ◽  
Brendan Heiden ◽  
Nicholas Pagani ◽  
Melissa M. Shaw ◽  
Sydney Shuff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Positive Breast Cancer

scholarly journals The role of abemaciclib in treatment of advanced breast cancer

2018 ◽  
Vol 10 ◽  
pp. 175883591877692 ◽  
Author(s):  
Amelia McCartney ◽  
Erica Moretti ◽  
Giuseppina Sanna ◽  
Marta Pestrin ◽  
Emanuela Risi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Endocrine Resistance ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Advanced Breast ◽  
Significant Activity ◽  
Epidermal Growth

Until recently, the mainstay of treatment in the majority of hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative advanced breast cancer (ABC) has consisted of single-agent endocrine therapy (ET). However, as understanding of endocrine resistance has grown, newer targeted agents have come to the fore. Inhibition of cyclin-dependent kinase complexes 4 and 6 (CDK4/6) combined with ET has shown significant activity in HR+ HER2− ABC, with impressive results in terms of progression-free survival (PFS) when compared with ET alone. This review summarizes the seminal findings pertaining to CDK4/6 inhibition in this population, specifically focusing on abemaciclib, contrasted with palbociclib and ribociclib. Potential directions for future studies are discussed, as a way of addressing outstanding issues such as establishing optimal treatment sequencing and agent combinations, appropriate patient selection to derive maximal benefits, predictive biomarkers and the employment of CDK4/6 inhibition beyond the ABC setting.

CTNND1 to mediate bone metastasis of triple-negative breast cancer via regulating CXCR4.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13045-e13045
Author(s):  
Chang Gong ◽  
Qun Lin ◽  
Xiaolin Fang ◽  
Wenguo Jiang ◽  
Jun Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
High Throughput ◽  
Triple Negative Breast Cancer ◽  
High Throughput Sequencing ◽  
Triple Negative ◽  
Mtor Pathway ◽  
Tissue Samples

e13045 Background: Compared to lumial breast cancer, the proporation of triple-negative breast cancer (TNBC) with bone metastases (BMs) is relatively low and few data focusing on the mechanism of the BMs in TNBC are available, Here, we screened that CTNND1 was associated with BMs of TNBC by integrating high-throughput sequencing, and further investigated the role of CTNND1 in BMs of TNBC in vitro. Methods: TNBC tissue samples with only BMs (n = 6) and without any metastasis (n = 10) were tested using high-throughput sequencing and 11 differentially expressed relative genes were identified. We then quantified these 11 genes in normal breast tissue samples (n = 26), TNBC tissue samples with only BMs (n = 10), TNBC tissue samples without any metastasis (n = 88) as well as luminal tissue samples with BMs（n = 10）through qPCR and immunohistochemical staining (IHC). The effects of knocking down CTNND1 on the interaction between TNBC cells and osteoblasts were examined by cell adhesion, transwell migration and matrigel invasion assays. To explorethe role of CTNND1 in mediating bone metastasis in TNBC, we used RNA-sequencing to find out the relative downstream gene CXCR4 and PI3K-AKT-mTOR pathway and verified it in vitro by Western Blotting. Results: Combining our high-throughput sequencing data, qPCR and IHC in clinical tissue samples, we verified that CTNND1 was decreased in TNBC patients with bone metastasis compared to normal tissue and luminal tissue with BMs. Knocking down of CTNND1 in TNBC cells including MDA-MB-231, MDA-MB-468 and BT549 weakened cells adhesion, but facilitated cells migration and invasion. Mechanically, knocking down of CTNND1 upregulated CXCR4 via activating PI3K-AKT-mTOR pathway in TNBC but not luminal and HER2- positive breast cancer cells lines. Conclusions: CTNND1 mediates bone metastasis in triple-negative breast cancer via regulating CXCR4.CTNND1 may serve as a potential predictor of bone metastasis for TNBC patients.

Sign in / Sign up

Export Citation Format

Share Document