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Oncotarget: LINC00520 is induced by Src, STAT3, and PI3K in breast cancer


FOR IMMEDIATE RELEASE
2020-12-20

Here is a link to a video interview with Dr. Whitney S. Henry about this research on the Oncotarget YouTube Channel

Oncotarget published "LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer" which reported that the authors 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, their 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 highlights that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype.

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 Oncotarget 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.

These Oncotarget 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.

Dr. Alex Toker from Harvard Medical School and John L. Rinn from Harvard University as well as The Broad Institute of MIT and Harvard said, "Cancer is largely driven by genetic alterations, which lead to the deregulation of gene networks that typically govern normal cellular homeostasis."

Gene expression profiling of various disease model systems has proven to be a powerful approach for identifying candidate lncRNAs implicated in cancer.

The first cancer-associated lncRNAs to be identified using differential expression profiling of prostate tumors and normal tissue, were prostate cancer associated 3 which is currently used as a biomarker for prostate cancer, and prostate-specific transcript 1 which is implicated in androgen receptor transcriptional activation.

Figure 6: Heat map showing expression profile of MCF10A cells expressing LINC00520. a. All genes (1693 genes) depicted in the heat map are upregulated in MCF10A-Src transformed cells. Abbreviations: UTC - Untransformed MCF10A cells; AC006262.6 is a lncRNAs that is not involved in transformation (negative control). Scale bar shows log2 row median centered expression values. b. GO analysis of a subset of genes that are upregulated upon ectopic expression of LINC00520 in MCF10A cells (grey line in heat map denotes top 291 genes used for analysis).

Differential expression profiling has also led to the discovery of the nuclear lncRNA metastasis-associated lung adenocarcinoma transcript 1, as one of the first lncRNAs to be ascribed a role as a potential prognostic biomarker for lung cancer survival.

Today the understanding of lncRNA biology is far from complete and the identification, regulation and functional characterization of lncRNAs involved in breast cancer pathogenesis may provide novel opportunities for differential diagnoses and therapeutic interventions.

Here they identify the novel lncRNA LINC00520 in breast cancer using two independent systems of cellular transformation driven by oncogenic v-Src and mutant PIK3CA, respectively.

The Henry Research Team concluded in their Oncotarget Priority Research Paper, "this study supports the accumulating evidence that lncRNAs may function to modulate human cancer pathogenesis. It points to a role for lncRNAs in the mechanism of action of critical oncogenes, namely Src, PI3K and STAT3. To our knowledge, this is the first study that investigates the regulation and biological function of LINC00520. It also implicates the first lncRNA identified as a downstream effector of the PI3K pathway. Future studies will dissect the entire complement of LINC00520 biology and its significance in processes critical for breast cancer initiation and progression."

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DOI - https://doi.org/10.18632/oncotarget.11962

Full text - https://www.oncotarget.com/article/11962/text/

Correspondence to - Alex Toker - atoker@bidmc.harvard.edu and John L. Rinn - john_rinn@harvard.edu

Keywords - lncRNA, Src, PI3K, breast cancer, LINC00520

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