Abstract
Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration. All these cellular changes were reversed by ectopic expression of hnRNP-L. Deletion of hnRNP-L resulted in decreased expression of Bcl-2, enhanced expression of caspases-3, -6 and -9 and inhibition of the MAPK signaling pathway. These findings demonstrate that hnRNP-L contributes to poor prognosis and tumor progression of BC by inhibiting the intrinsic apoptotic signaling and enhancing MAPK signaling pathways.
Highlights
Bladder cancer (BC) is one of the most common malignant neoplasms in urological system and considered as the fourth most prevalent neoplasm in males [1]
heterogeneous nuclear ribonucleoprotein L (HnRNP-L) expression was detected in tissue microarray (TMA) containing 155 cases of archived paraffin-embedded bladder cancer specimens by immunohistochemical staining (IHC)
The multivariate analysis of the Cox regression model, Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) expression (p = 0.002, Hazard Ratio (HR) = 5.038) and tumor clinical stage (p = 0.018, HR = 8.456) was confirmed to be independent prognosis factors for bladder cancer patients (Table 3). These results suggested that hnRNP-L may be a probable independent predictor in patients with bladder cancer
Summary
Bladder cancer (BC) is one of the most common malignant neoplasms in urological system and considered as the fourth most prevalent neoplasm in males [1]. It is urgent to identify novel biomarkers and therapeutic targets for the prognostic prediction and treatment of bladder cancer
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