Abstract
PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.
Highlights
Erefore, understanding the molecular mechanisms underlying tumor progression and finding specific prognostic biomarkers are clinically important
Significant technological progress has been made for the early diagnosis and prognosis of papillary thyroid carcinoma (PTC), most screening techniques such as biopsy, ultrasound scan, and low-dose spiral CT scans are associated with some risk of overdiagnosis and false positives [2]. e mechanisms underlying PTC development, progression, and recurrence remain largely unknown. erefore, identification of preventive strategies and therapeutic targets is urgent for PTC patients
Recent studies demonstrated that Pre-B-cell leukemia homeobox 3 (PBX3) acts as an oncogenic gene and participates in tumorigenesis, progression, and metastasis in many human malignancies including leukemia, multiple myeloma, gastrointestinal cancer, and prostate cancer [19]
Summary
Erefore, understanding the molecular mechanisms underlying tumor progression and finding specific prognostic biomarkers are clinically important. PBX3 expression is upregulated in some solid cancers and acts as a critical transcriptional switch for hepatoma stem cells [10,11,12]. Overexpression of PBX3 induces epithelial-mesenchymal transition and promotes invasion and metastasis of gastric, and colorectal cancer cells [13,14,15]. Elevated expression of PBX3 is associated with indolent progression to castration-resistant prostate cancer [16, 17]. Targeting HOXA9/ PBX3 interaction has been suggested as a new therapeutic strategy to treat leukemia, gastrointestinal cancer, and nonsmall cell lung cancer [5, 18, 19]. We detected PBX3 expression in tissues from PTC patients and highlighted its new role in PTC cell proliferation and progression
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