Abstract
Long non-coding RNAs (LncRNA) as the key regulators in all stages of tumorigenesis and metastasis. However, the underlying mechanisms are largely unknown. Here, we report a lncRNA RP11-214F16.8, which renamed Lnc-PCIR, is upregulated and higher RNA level of Lnc-PCIR was positively correlated to the poor survival of patients with triple negative breast cancer (TNBC) tissues. Lnc-PCIR overexpression significantly promoted cell proliferation, migration, and invasion in vitro and in vivo. RNA pulldown, RNA immunoprecipitation (RIP) and RNA transcriptome sequencing technology (RNA-seq) was performed to identify the associated proteins and related signaling pathways. Mechanistically, higher Lnc-PCIR level of blocks PABPC4 proteasome-dependent ubiquitination degradation; stable and highly expressed PABPC4 can further increase the stability of TAB3 mRNA, meanwhile, overexpression of Lnc-PCIR can disrupt the binding status of TAB3 and TAB2 which lead to activate the TNF-α/NF-κB pathway in TNBC cells. Our findings suggest that Lnc-PCIR promotes tumor growth and metastasis via up-regulating the mRNA/protein level of TAB3 and PABPC4, activating TNF-α/NF-κB signaling pathway in TNBC.
Highlights
Breast cancer is the most frequently diagnosed malignancy in women worldwide and is the second leading cause of cancer-related death in the United States [1, 2]
In order to identify Long non-coding RNAs (lncRNAs) that play a role in Triple negative breast cancer (TNBC), we used RNA-sequencing (RNA-seq) data from 1084 patients available in the TCGA database (The Cancer Genome Atlas)
Using differentially expressed gene analysis, we identified a subset of lncRNAs overexpressed with clinically relevant in the TNBC subtype compared to normal tissue (Figures 1A, B and Supplementary Excel 1)
Summary
Breast cancer is the most frequently diagnosed malignancy in women worldwide and is the second leading cause of cancer-related death in the United States [1, 2]. Expression of the estrogen receptor (ER), progesterone receptor (PR), and amplification of the HER2 gene define the main breast cancer subtypes in terms of prognostic and therapeutic intervention [3]. HER2 [4].Therapies commonly used in other breast cancer subtypes are not suitable for TNBC, and treatment options are largely limited to conventional genotoxic chemotherapy [5, 6]. LncRNAs have been implicated to regulate a range of biological functions, such as genomic imprinting and transcriptional regulation, plays a critical role in tumorigenesis and metastasis [10,11,12]. Numerous studies have showed the important role of NF-kB pathway as a link between inflammation and tumorigenesis [13]. The mechanism of overexpressed TAB3 in the process of TNBC remains unclear
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