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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.

SUBMITTER: DeVaux RS

PROVIDER: S-EPMC7263938 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

DeVaux Rebecca S RS Ropri Ali S AS Grimm Sandra L SL Hall Peter A PA Herrera Emilio O EO Chittur Sridar V SV Smith William P WP Coarfa Cristian C Behbod Fariba F Herschkowitz Jason I JI

Journal of cellular biochemistry 20200107 7

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). ...[more]

PMID: 31907974

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Project description:OBJECTIVES:The long-noncoding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes in glioblastoma (GBM) tissues. However, the expression pattern and biological function of lncRNAs remain largely unknown. Here, for the first time, the effects of lncRNA lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) on GBM progression both in vitro and in vivo are investigated. MATERIALS AND METHODS:Expression profiles of LEF1-AS1 in GBM specimens were investigated by bioinformatics analyses. LEF1-AS1 expression in GBM tissues was detected using a quantitative polymerase chain reaction. LEF1-AS1 expression was inhibited by transfecting the LEF1-AS1-specific small interfering RNAs (siRNAs) and stable cell lines established were inhibited by transfecting si-LEF1-AS1 viruses. The Cell Counting Kit-8, ethynyl deoxyuridine, and colony formation assay were used to examine proliferation function. The flow cytometry detected cell-cycle change and apoptosis. Migration effects were detected by a Transwell assay. The tumor xenografts and immunohistochemistry were performed to evaluate tumor growth in vivo. RESULTS:In this study, LEF1-AS1 expression was found significantly upregulated in GBM specimens compared with normal tissues. The 5-year overall survival in GBM patients from The Cancer Genome Atlas with high expression of LEF1-AS1 was inferior to that with low expression. It was confirmed that expression of LEF1-AS1 was higher in GBM tissues than normal ones. Knockdown of LEF1-AS1 significantly inhibited the malignancy of GBM cells, including proliferation and invasion, and promoted cell apoptosis. The result of Western blot assays indicated that knockdown of LEF1-AS1-mediated tumor suppression in GBM cells may be via the reduction of ERK and Akt/mTOR signaling activities. Finally, the in vivo experiment also demonstrated that knockdown LEF1-AS1 inhibited the growth-promoting effect of LEF1-AS1 of U87 cells. CONCLUSION:Our result indicated that lncRNA LEF1-AS1 acts as an oncogene in GBM and may be a pivotal target for this disease.

Dataset Information

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

Publications

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

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