LncRNA BCAR4 up-regulates EGFR and thus promotes human thyrocyte proliferation

Abstract

This study establishes that BCAR4 has pro-proliferative effects on normal thyroid cells. BCAR4 up-regulation promotes proliferation and suppresses apoptosis of NTHY-ORI 3-1 cells and human primary thyrocytes, and EGFR is highly expressed in BCAR4 over-expressing-cells. In contrast, BCAR4 up-regulation did not modulate cell viability or cell cycle progression when EGFR was knocked-down. Further, the phosphorylated forms of PI3K, AKT, mTOR and p70S6K were up-regulated by BCAR4 up-regulation, and the alteration in these kinases induced by BCAR4 up-regulation was abolished when EGFR was knocked-down. This study therefore revealed the pro-proliferative role of lncRNA BCAR4 in NTHY-ORI 3-1 cells and human primary thyrocytes; where BCAR4 accelerated thyroid cells proliferation by EGFR up-regulation and the modulation of PI3K/AKT/mTOR signaling. These findings indicate that targeting BCAR4 has potential in hyperthyroidism treatment.

<p>Long Noncoding RNA LINC00265 Targets EGFR and Promotes Deterioration of Colorectal Cancer: A Comprehensive Study Based on Data Mining and in vitro Validation</p>

“…We also found that the downregulation of LINC00265 could decrease the expression level of EGFR. Consistent with us, Tan found that lncRNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma,29 Zhai reported lncRNA BCAR4 accelerated thyroid cells proliferation by EGFR up-regulation 30. However, LncRNAs do not directly encode protein, they play multiple roles through the mediation of mRNAs or microRNAs.…”

Individualized Prediction of Survival by a 10-Long Non-coding RNA-Based Prognostic Model for Patients With Breast Cancer

“…The newly developed 10-lncRNA signature contained two known lncRNAs (BCAR4 and LINC00536). BCAR4 (BC antiestrogen resistance 4) originally was found to participate in the development of resistance to antiestrogens in BC, whose expression is associated with proliferation, metastasis, and invasion of multiple tumors (45)(46)(47)(48). LINC00536, a newly identified lncRNA by Nakajima in 2014, was found to be highly expressed in bladder cancer and promoted the tumorigenesis and development of bladder cancer partly by modulating the Wnt3a/β-catenin signaling (49).…”

Association of LncRNA‐GAS5 gene polymorphisms and PBMC LncRNA‐GAS5 level with risk of systemic lupus erythematosus in Chinese population

“…Recent studies have shown that lncRNAs, which were previously considered as mere transcriptional noise, regulate gene expression at the transcriptional levels 12 . The pathogenesis of several autoimmune inflammatory disorders, such as rheumatoid arthritis, SLE, multiple sclerosis, ulcerative colitis, hyperthyroidism and chronic liver disease, are known to involve lncRNAs 13‐15 . The aberrant expression of GAS5, a new type of lncRNAs, has been reported in SLE patients and animal models 16,17 .…”

“…12 The pathogenesis of several autoimmune inflammatory disorders, such as rheumatoid arthritis, SLE, multiple sclerosis, ulcerative colitis, hyperthyroidism and chronic liver disease, are known to involve lncRNAs. [13][14][15] The aberrant expression of GAS5, a new type of ln-cRNAs, has been reported in SLE patients and animal models. 16,17 The lncRNA-mRNA co-expression analysis showed that LncRNA-GAS5, lnc0640 and lnc5150 were involved in SLE pathogenesis through the mitogen-activated protein kinase pathway (MAPK), and the LncRNA-GAS5 in plasma could be used as SLE biomarkers.…”