LncRNA PCIR Is an Oncogenic Driver via Strengthen the Binding of TAB3 and PABPC4 in Triple Negative Breast Cancer

Wenhui Guo; Jingyi Li; Haobo Huang; Fangmeng Fu; Yuxiang Lin; Chuan Wang

doi:10.3389/fonc.2021.630300

LncRNA PCIR Is an Oncogenic Driver via Strengthen the Binding of TAB3 and PABPC4 in Triple Negative Breast Cancer

Front Oncol. 2021 May 3:11:630300. doi: 10.3389/fonc.2021.630300. eCollection 2021.

Authors

Wenhui Guo^{1

2

3}, Jingyi Li⁴, Haobo Huang⁵, Fangmeng Fu^{1

2

3}, Yuxiang Lin^{1

2

3}, Chuan Wang^{1

2

3}

Affiliations

¹ Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
² Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
³ Breast Cancer Institute, Fujian Medical University, Fuzhou, China.
⁴ College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
⁵ Department of Blood Transfusion, Fujian Medical University Union Hospital, Fuzhou, China.

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.

Keywords: RP11-214F16.8/Lnc-PCIR; TGF-beta activated kinase 1 (MAP3K7) binding protein 3; TNF-α/NF-κB signaling pathway; long non-coding RNA; poly(A) binding protein cytoplasmic 4.