While cancer-associated fibroblasts (CAFs) in the tumour microenvironment may play important roles in bladder cancer (BCa) progression, their impacts on BCa chemoresistance remain unclear. Using human BCa samples, we found that tumour tissues possessed more CAFs than did adjacent normal tissues. Both the presence of CAFs in the BCa stroma and the expression of ERβ in BCa contribute to chemoresistance, and CAFs and BCa cells interact to affect ERβ expression. In vitro co-culture assays demonstrated that compared with normal bladder cells, BCa cells had a higher capacity to induce the transformation of normal fibroblasts into CAFs. When BCa cells were co-cultured with CAFs, their viability, clone formation ability and chemoresistance were increased, whereas their apoptotic rates were downregulated. Dissection of the mechanism revealed that the recruited CAFs increased IGF-1/ERβ signalling in BCa cells, which then led to the promotion of the expression of the anti-apoptotic gene Bcl-2. Blocking IGF-1/ERβ/Bcl-2 signalling by either an shRNA targeting ERβ or an anti-IGF-1 neutralizing antibody partially reversed the capacity of CAFs to increase BCa chemoresistance. The in vivo data also confirmed that CAFs could increase BCa cell resistance to cisplatin by increasing ERβ/Bcl-2 signalling. The above results showed the important roles of CAFs within the bladder tumour microenvironment, which could enhance BCa chemoresistance.

No abstract

Background: Prostate cancer (PCa) is a prevalent and deadly cancer worldwide. Considering the malignant progression and therapeutic resistance of PCa, further dissection of the underlying mechanisms and exploration of novel therapeutic targets for PCa are urgently needed. The long noncoding RNA HOTTIP has recently been revealed as an oncogenic regulator in different cancers; however, whether HOTTIP is involved in PCa remains poorly understood. Here, we examined the crucial roles of HOTTIP in the proliferation and chemoresistance of PCa.Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the HOTTIP messenger RNA (mRNA) levels in PCa samples from patients and PCa cells. Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell cycle and flow cytometry assays were performed to investigate the proliferation and cisplatin-resistance of PCa cells with silenced HOTTIP compared with a negative control. We applied Western blotting, qRT-PCR and a TOP/FOP assay to explore the relevant mechanisms.Results: In this study, we found that the HOTTIP mRNA levels were increased in the PCa patient samples and PCa cell lines compared with the controls. The knockdown of HOTTIP not only inhibited the proliferation of PCa cells but also facilitated cell cycle arrest and chemosensitivity to cisplatin. Furthermore, the qRT-PCR, Western blotting, TOP/FOP assays, MTT assay, and flow cytometry revealed that Wnt/β-catenin signaling was related to the regulation of HOTTIP in cell proliferation, cell cycle arrest, and chemoresistance to cisplatin in PCa. Conclusion: Taken together, our findings suggest that HOTTIP may be a potent therapeutic target for PCa, and HOTTIP inhibitors might be regarded as effective strategies for PCa therapy. K E Y W O R D S chemoresistance, HOTTIP, long noncoding RNA (lncRNA), proliferation, prostate cancer (PCa), Wnt/β-catenin J Cell Biochem. 2019;120:8965-8974. wileyonlinelibrary.com/journal/jcb of the long noncoding RNA HOTTIP inhibits cell proliferation and enhances cell sensitivity to cisplatin by suppressing the Wnt/β-catenin pathway in prostate cancer. J Cell Biochem. 2019;120:8965-8974.

T he incidence of prostate cancer (PCa) has increased by 42% worldwide since 2007 (1). Early and accurate diagnosis is of great importance for prognosis and for planning treatment. In clinical routine, the likelihood of clinically significant PCa is assessed by using the Prostate Imaging Reporting and Data System (PI-RADS), which incorporates anatomic and functional information acquired by using multiparametric MRI (2,3). This diagnostic MRI pathway with subsequent biopsy-based histopathologic confirmation is the recommended strategy in patients suspected to have PCa (4). However, PI-RADS version 2 has limitations including moderate interreader agreement, diagnostic challenges due to overlapping imaging features between PCa and benign prostatic disease, and relatively high false-negative and false-positive rates (5-12). The 2019 update, PI-RADS version 2.1 (13), has only slightly improved interreader variability and diagnostic performance for lesions located in the transition zone (TZ) (12). Therefore, new quantitative imaging markers are desirable for further improving depiction and characterization of PCa (13,14). Tomoelastography, a multifrequency MR elastography technique, has been recently introduced for cancer imaging (15,16). Two mechanical parameters are evaluated with tomoelastography: shear-wave speed (c) and phase angle of the shear modulus (w), which are surrogate markers of stiffness and fluidity, respectively. Within the liver, these parameters provide information regarding the viscoelastic