Functional Characterization of lncRNA152 as an Angiogenesis-Inhibiting Tumor Suppressor in Triple-Negative Breast Cancers

Abstract

Long non-coding RNAs have been implicated in many of the hallmarks of cancer. Herein, we found that the expression of lncRNA152 (lnc152; a.k.a. DRAIC), which we annotated previously, is highly upregulated in luminal breast cancer (LBC) and downregulated in triple-negative breast cancer (TNBC). Knockdown of lnc152 promotes cell migration and invasion in LBC cell lines. In contrast, ectopic expression of lnc152 inhibits growth, migration, invasion, and angiogenesis in TNBC cell lines. In mice, lnc152 inhibited the growth of TNBC cell xenografts, as well as metastasis of TNBC cells in an intracardiac injection model. Transcriptome analysis of the xenografts indicated that lnc152 downregulates genes controlling angiogenesis. Using pull down assays followed by LC-MS/MS, we identified RBM47, a known tumor suppressor in breast cancer, as a lnc152-interacting protein. The effects of lnc152 in TNBC cells are mediated, in part, by regulating the expression of RBM47. Collectively, our results demonstrate that lnc152 is an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC. Implications: This study identifies lncRNA152 as an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC by upregulating the expression of the tumor suppressor RBM47; as such, lncRNA152 may serve as a biomarker to track aggressiveness of breast cancer, as well as therapeutic target for treating TNBC.

Construction of a predictive model for breast cancer metastasis based on lncRNAs

“…Non-coding RNAs account for >90% of the entire human gene transcripts, participate in almost all epigenetic regulation, and play an important role in the complex life activities of advanced eukaryotes (16,17). Abnormal expressions of lncRNAs are involved in the process, metastasis, and prognosis of breast cancer (18)(19)(20). LncRNAs may play a role in promoting or inhibiting tumorigenesis and progression.…”

“…acts as an angiogenesis inhibitor in triple-negative breast cancer that impedes cancer cell metastasis (20).…”

An Angiogenesis-Related lncRNA Signature Is Associated with Prognosis and Tumor Immune Microenvironment in Breast Cancer

“…In most tumors, microvascular formation is a prognostic marker for metastasis, recurrence, and survival [ 24 , 25 ]. Angiogenesis-related genes have been reported to be potential prognostic markers associated with BC, and integrating these genes has important implications for understanding and assessing tumor progression [ 1 , 26 , 27 , 28 , 29 , 30 ]. Among these genes, lncRNAs also play an essential role [ 26 , 28 , 31 ].…”

LncRNA 152 attenuates lipopolysaccharide‐induced acute kidney injury in rats by regulating the FGF23/Klotho/MAPK axis

“…Originally, LncRNA 152 was found to play an oncogenic role in prostate cancer. 24 Further studies have revealed that LncRNA 152 regulates cell proliferation, invasion, migration and autophagy, and is associated with a variety of cancers. 25,26 Besides, the expression of LncRNA 152 is positively associated with the disease-free survival in renal cell carcinoma patients.…”

“…LncRNA 152, also known as LncRNA DRAIC, is a 1.7 kb LncRNA located on human chromosome 15q23. Originally, LncRNA 152 was found to play an oncogenic role in prostate cancer 24 . Further studies have revealed that LncRNA 152 regulates cell proliferation, invasion, migration and autophagy, and is associated with a variety of cancers 25,26 .…”