Abstract
BackgroundBladder cancer (Bca) is the most common malignant tumor of the urinary system. Circular RNAs (circRNAs) have been recognized as key regulators in tumorigenesis. However, the molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown.MethodsWe detected the expression level of circular RNA TAF4B (circTAF4B) by qRT-PCR assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Wound healing and Transwell assays were performed to measure cell migration and invasion capability. Moreover, we performed qRT-PCR and western blotting assays to determine the expression levels of epithelial-mesenchymal transition (EMT) markers. A nuclear/cytoplasmic fractionation assay was used to measure the subcellular location of circTAF4B. RNA pull-down and dual-luciferase reporter assays were used to detect the target microRNA of circTAF4B. A mouse xenograft model was produced to analyze the effect of circTAF4B on the tumorigenesis of BCa.ResultsIn this study, we identified a novel circular RNA, circTAF4B, that is significantly upregulated in BCa and correlated with poor prognosis. Downregulated circTAF4B abolished the growth, metastasis and EMT process in BCa cells. Mechanistically, we found that circTAF4B facilitated the expression of transforming growth factor A (TGFA) by sponging miR-1298-5p. Finally, circTAF4B enhanced the proliferation and EMT process of BCa cells in vivo.ConclusionIn summary, our study demonstrated that circTAF4B played a carcinogenic role in the growth, metastasis, and EMT process of BCa by regulating the miR-1298-5p/TGFA axis. Thus, circTAF4B may become a diagnostic and therapeutic target for BCa.
Highlights
Bladder cancer (Bca) is the ninth most common cancer in the world and one of the most common malignancies of the urinary system [1, 2]
We focused on circ_0047322 by screening RNASequence data from a previous study [25]. circ_0047322 is derived from the TATA-box binding protein (TBP)-associated factor 4B (TAF4B) gene and was identified as circTAF4B. circTAF4B was significantly upregulated in BCa tissues and closely correlated with poor prognosis in BCa patients
Our findings revealed a novel potential mechanism by which the circTAF4B/miR-1298-5p/transforming growth factor A (TGFA) signaling pathway is involved in the tumorigenesis and metastasis of BCa
Summary
Bladder cancer (Bca) is the ninth most common cancer in the world and one of the most common malignancies of the urinary system [1, 2]. BCa is divided into two types based on the depth of tumor invasion: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) [4,5,6]. MIBC accounts for approximately 25% of this disease, nearly half of patients develop tumor metastasis and have a poor prognosis [7, 8]. The 5-year survival rate of BCa patients remains at a low level despite the development of surgical and chemotherapy treatments in the past decade [9, 10]. The mechanisms underlying BCa development and metastasis remain unknown. The molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown
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