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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer
Whitney S Henry1, David G Hendrickson2,3, Francisco Beca1
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Abstract:
Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNA-mediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.
Insights
A novel long non-coding RNA, LINC00520, is upregulated by oncogenes like v-Src and PI3K in breast cancer cells. Its depletion impairs cell migration, suggesting a role in breast cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are crucial in cellular functions and diseases, including cancer.
- Oncogenic signaling pathways play a significant role in breast cancer pathogenesis.
Purpose of the Study:
- To identify novel lncRNAs involved in breast cancer development.
- To characterize the role and regulation of LINC00520 in breast cancer.
Main Methods:
- Global gene expression profiling of mammary epithelial cells.
- Analysis of LINC00520 expression in response to oncogenic signaling (v-Src, PI3K, STAT3).
- Functional assays including cell migration and 3D invasion, and RNA sequencing.
Main Results:
- Identified LINC00520 as a novel lncRNA upregulated by v-Src and PI3K signaling, dependent on STAT3.
- LINC00520 is elevated in a subset of human breast carcinomas, particularly basal-like subtype.
- Depletion of LINC00520 reduced cell migration and invasion, and altered gene expression profiles.
Conclusions:
- LINC00520 is regulated by key oncogenic pathways (Src, PI3K, STAT3) in breast epithelial cells.
- LINC00520 contributes to breast cancer cell migration and invasion.
- LINC00520 is a potential therapeutic target and biomarker for breast cancer.
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