Long noncoding RNA BHLHE40-AS1 promotes early breast cancer progression through modulating IL-6/STAT3 signaling

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer, but predicting progression is challenging.
• Current aggressive treatment of all DCIS leads to overdiagnosis and overtreatment.
• Identifying drivers of DCIS progression to invasive ductal carcinoma (IDC) is crucial.

Purpose of the Study:

• To identify functional determinants of DCIS progression to IDC.
• To investigate the role of long noncoding RNAs in breast cancer progression.

Main Methods:

• Analysis of contiguous DCIS and IDC lesions from five patients.
• Quantification of BHLHE40-AS1 expression.
• Assessment of BHLHE40-AS1's effects on cell proliferation, motility, and invasion.
• Investigation of molecular mechanisms involving IL-6/STAT3 signaling and interleukin enhancer-binding factor 3.

Main Results:

• BHLHE40-AS1 expression increases with disease progression from DCIS to IDC.
• BHLHE40-AS1 expression promotes DCIS cell proliferation, motility, and invasive potential.
• BHLHE40-AS1 modulates IL-6/STAT3 activity and a proinflammatory cytokine signature, partly via interaction with interleukin enhancer-binding factor 3.

Conclusions:

• BHLHE40-AS1 is a key driver of early breast cancer progression.
• BHLHE40-AS1 facilitates DCIS to IDC transition by engaging STAT3 signaling.
• BHLHE40-AS1 contributes to an immune-permissive microenvironment, promoting tumor progression.