Long noncoding RNA BHLHE40‐AS1 promotes early breast cancer progression through modulating IL‐6/STAT3 signaling
Abstract
Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive breast cancer. Only a small percentage of DCIS cases are predicted to progress; however, there is no method to determine which DCIS lesions will remain innocuous from those that will become invasive disease. Therefore, DCIS is treated aggressively creating a current state of overdiagnosis and overtreatment. There is a critical need to identify functional determinants of progression of DCIS to invasive ductal carcinoma (IDC). Interrogating biopsies from five patients with contiguous DCIS and IDC lesions, we have shown that expression of the long noncoding RNA BHLHE40‐AS1 increases with disease progression. BHLHE40‐AS1 expression supports DCIS cell proliferation, motility, and invasive potential. Mechanistically, BHLHE40‐AS1 modulates interleukin (IL)‐6/signal transducer and activator of transcription 3 (STAT3) activity and a proinflammatory cytokine signature, in part through interaction with interleukin enhancer‐binding factor 3. These data suggest that BHLHE40‐AS1 supports early breast cancer progression by engaging STAT3 signaling, creating an immune‐permissive microenvironment.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 07, 2020
- Source ID
- 10.1002/jcb.29621
Entities
People
- Ali S. Ropri
- Cristian Coarfa
- Emilio O. Herrera
- Fariba Behbod
- Jason I. Herschkowitz
- Peter A. Hall
- Rebecca Sinnott
- Sandra L. Grimm
- Sridar V. Chittur
- William P. Smith
Organizations
- Baylor College of Medicine
- Breast Cancer Alliance
- Cancer Prevention and Research Institute of Texas
- Institut National du Cancer
- National Institute of Environmental Health Sciences
- Queen's University
- Spackenkill High School
- Susan G. Komen for the Cure
- The Breast Cancer Research Foundation
- United States Department of Defense
- University of Kansas