[Corrigendum] The targeting of MTDH by miR­145­5p or miR­145­3p is associated with prognosis and regulates the growth and metastasis of prostate cancer cells.

Following the publication of the above article, an interested reader drew to the authors' attention that the Transwell invasion assay images in Fig. 3B on p. 1961 representing the Con/PWR­1E and the PC­3/siMTDH experiments contained overlapping sections, such that they appeared to have been derived from the same original source, even though they were intending to have shown the results from differently performed experiments. Similarly, in Fig. 8A on p. 1965, the representative images selected for the PC­3/miR­145­3p and LNCaP/miR­145­3p data panels were also found to contain overlapping sections. After having consulted their original data, the authors realized that these errors had occurred while compiling the affected figure parts. The revised versions of Figs. 3 and 8, containing the data from one of the repeated experiments in Fig. 3B and 8A, are shown on the next two pages. Concerns about the western blots featured in Figs. 4C and D and 9F were also raised by the interested reader; upon querying these with the authors, however, they were able to provide the full blots in these cases, thereby confirming their authenticity. The authors regret that these errors went unnoticed prior to publication, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 54: 1955­1968, 2019; DOI: 10.3892/ijo.2019.4782].

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Ningmitai capsule promotes calculi expulsion after RIRS for 10-20-mm upper urinary stones: a multicenter, prospective, randomized controlled trial.

To evaluate the efficacy and safety of the use of Ningmitai capsule as an adjunctive stone expulsion therapy after RIRS. All patients were diagnosed with upper urinary tract calculi measuring 10-20 mm. The patients who successfully underwent RIRS were randomly assigned to the NMT capsule group (Ningmitai capsule, 1.52 g, three times daily) or the control group for 4 weeks based on the random number table method. The primary endpoints were the stone expulsion rate (SER) and stone-free rate (SFR). The average stone expulsion time (SET), average stone-free time (SFT) and complications were recorded. Between July 2, 2019, and December 17, 2020, 220 participants successfully underwent RIRS across 6 centers; 123 of them were randomized according to the exclusion criteria, and 102 (83%) were included in the primary analysis. The SERs on the 3rd, 7th, 14th and 28th days were significantly increased in the NMT capsule group compared with the control group (78.95% vs. 31.11%, 92.98% vs. 55.56%, 94.74% vs. 64.44%, 100% vs. 82.22%, respectively, p < 0.05). The SFRs on the 3rd and 7th days were not different (p > 0.05), while those on the 14th and 28th days were higher in the NMT capsule group (63.16% vs. 24.44% and 92.98% vs. 68.89%, p < 0.05). The average SET and average SFT of the NMT capsule group were remarkably shorter than those of the control group (p < 0.001). During the follow-up period, there were no significant differences in urine RBC counts between the two groups (p > 0.05). The urine WBC counts of the NMT capsule group were significantly lower than those of the control group on the 14th day (p = 0.011), but there was no difference on the 3rd, 7th or 28th day (p > 0.05). The analgesic aggregate of the NMT capsule group was also much lower (p = 0.037). There were no significant differences in adverse events (p > 0.05), and they improved significantly without sequelae. This study indicated that NMT capsules can significantly promote stone clearance and are more effective and safer for upper urinary calculi after RIRS.Trial registration Chinese Clinical Trial Registration No. ChiCTR1900024151.Date of registration June 28, 2019.

Ursolic acid treats renal tubular epithelial cell damage induced by calcium oxalate monohydrate via inhibiting oxidative stress and inflammation.

Ursolic acid (UA) has been proved to have antioxidant and anti-inflammatory effects. However, it is not clear whether it has a protective impact on kidney damage induced by crystals of calcium oxalate monohydrate (COM). This work aimed to make clear the potential mechanism of UA protecting COM-induced kidney damage. The results manifested that high- and low-dose UA reduced COM crystals in COM rats' kidney, down-regulated urea, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) levels in rat plasma, declined kidney tissue and HK-2 cell apoptosis, inhibited Bax expression but elevated Bcl-2 expression. Additionally, UA alleviated renal fibrosis in COM rats, repressed α-SMA and collagen I protein expressions in the kidney and COM rats' HK-2 cells, depressed COM-induced oxidative damage in vivo and in vitro via up-regulating Nrf2/HO-1 pathway, up-regulated SOD levels and reduced MDA levels, down-regulated TNF-α, IL-1ß, and IL-6 levels in vivo and in vitro via suppressing activation of TLR4/NF-κB pathway. In summary, the results of this study suggest that COM-induced renal injury can be effectively improved via UA, providing powerful data support for the development of effective clinical drugs for renal injury in the future.

LncRNA MCM3AP-AS1 Promotes Cell Proliferation and Invasion Through Regulating miR-543-3p/SLC39A10/PTEN Axis in Prostate Cancer.

OBJECTIVE: Long-chain noncoding RNAs (lncRNAs) are key players in a wide range of biological processes, especially the pathogenesis and development of tumors. LncRNA MCM3AP-AS1 has been demonstrated to be involved in the invasion of various tumors including prostate cancer (PCa). However, its functions in PCa have not been fully elucidated. METHODS: qRT-PCR was conducted to measure the expression levels of lncRNA MCM3AP-AS1 and miR-543-3p in PCa tissue samples and cell lines. The expression levels of E-cadherin and SLC39A10 proteins were detected by Western blots. CCK-8 test, cell scratch test and trans-well test were used to evaluate the proliferation, invasion and migration abilities of PCa cells, respectively. Annexin V-FITC/PI experiments were carried out to determine the status of apoptosis. Bioinformatics analysis and Luciferase assay were used to explore the relationship between lncRNA MCM3AP-AS1, miR-543-3p and SLC39A10. RESULTS: In PCa tissue samples and cell lines, lncRNA MCM3AP-AS1 was up-regulated while miR-543-3p was down-regulated. Over-expression of MCM3AP-AS1 could promote the proliferation and invasion of PCa cells. Correlation analysis showed that the expression of MCM3AP-AS1 and miR-543-3p was significantly and inversely correlated. We further verified that miR-543-3p inhibitor was able to reverse si-MCM3AP-AS1-mediated inhibitory effects on the PCa cell proliferation, migration and invasion through regulating the downstream protein axis SLC39A10/PTEN/Akt. Finally, in vivo experiments indicated that knocking down of MCM3AP-AS1 could largely reduce tumor volumes, and decreased the ratio of Ki67-positive cells and the expression of SLC39A10 in tumor samples. CONCLUSION: LncRNA MCM3AP-AS1 can promote the proliferation, migration and invasion abilities of PCa cells through regulating the miR-543-3p/SLC39A10/PTEN axis, which suggests that lncRNA MCM3AP-AS1 might be a potential target for prostate cancer therapy.

Dual delivery nanoscale device for miR-451 and adriamycin co-delivery to combat multidrug resistant in bladder cancer.

The outcome of current cancer therapy is usually impeded by complicated extracellular and intracellular barriers. Most importantly, untargeted distribution and multidrug resistance (MDR) are considered as two important difficulties responsible for the poor performance of many currently available drug delivery systems (DDS). As a result, in our study, we developed a cancer cell membrane (CM) coated calcium carbonate (CC) nanoparticles to co-delivery miR-451 with adriamycin (Adr) to address the dilemma occurred in the therapy of bladder cancer (MCC/R-A). The homologous CCM from MDR bladder cancer cells (BIU-87/Adr) was employed to increase targeted retention of DDS within the tumor tissue and to bypass the extracellular barriers. Moreover, the MDR of cancer cells was conquered through downregulation of P-gp expression using miR-451 since it was confirmed by previous reports that miR-451 could significantly downregulate the level of P-gp in MDR cells, which in turn elevated the cellular drug retention in BIU-87/Adr. Our in vitro and in vivo experiments have revealed that MCC/R-A showed a greatly enhanced therapeutic effect on BIU-87/Adr, which was superior than applying miR-451 or Adr alone. The preferable effect of MCC/R-A on conquering the MDR in bladder cancer provides a novel alternative for effective chemotherapy of MDR cancers.

Activated Wnt/ß-Catenin signaling contributes to E3 ubiquitin ligase EDD-conferred docetaxel resistance in prostate cancer.

Docetaxel is commonly used to treat hormone-refractory prostate cancer (HRPC), but its clinical efficacy is limited by drug resistance, with the molecular mechanisms remaining elusive. The E3 ubiquitin ligase EDD modifies substrate proteins through ubiquitination and is involved in the regulation of cell proliferation and tumorigenesis. However, its role in docetaxel resistance of prostate cancer is unknown. Here, we show that EDD is upregulated in docetaxel-resistant HRPC cells, as well as in human HRPC treated with docetaxel chemotherapy. Functionally, EDD knockdown resensitizes HRPC cells to docetaxel in vitro and in vivo, and in reverse, EDD overexpression promotes docetaxel resistance. We further show that the Wnt/ß-Catenin signaling is activated in docetaxel-resistant HRPC cells, which can be promoted by EDD. Finally, inhibiting Wnt signaling through ß-Catenin knockdown remarkably attenuates EDD-mediated docetaxel resistance, suggesting that the activated Wnt/ß-Catenin signaling is a key contributor to EDD-conferred docetaxel resistance in HRPC cells. Altogether, our study uncovers a positive role of EDD in docetaxel resistance in prostate cancer, and further links it with the regulation of Wnt/ß-Catenin signaling.

The targeting of MTDH by miR­145­5p or miR­145­3p is associated with prognosis and regulates the growth and metastasis of prostate cancer cells.

Studies have rarely been conducted on the role of miRNAs in prostate cancer (PCa) cell progression by directly targeting MTDH, at least to the best of our knowledge. Thus, the present study aimed to identify miRNAs closely related with metadherin (MTDH) and to determine their roles in PCa. For this purpose, the expression levels of MTDH in PCa tissues and cell lines were examined by RT­qPCR, immunohistochemistry and western blot analysis. By cell transfection, MTDH was either overexpressed in the normal prostate epithelial cell lines or silenced in tumor cell lines to determine cell viability, invasion and migration. Bioinformatics analysis, RT­qPCR, western blot analysis, dual­luciferase reporter assay and MTT assay were performed to identify direct the target of MTDH and to examine tumor cell viability. Rescue experiments using the PC­3 and LNCaP cells were carried out by MTT assay, scratch wound assay, Transwell assay, RT­qPCR and western blot analysis. Experiments were also conducted using 46 PCa human cancer and adjacent tissues, as wells as on 501 cases of PCa from the TCGA database. It was confirmed that the overexpression of MTDH was associated with a poor prognosis of patients. The overexpression of MTDH was found to promote the viability, invasion and migration of PCa cells. miR­145­5p and miR­145­3p identified from 16 miRNAs were found to be closely related to PCa and to be the targets of MTDH. Both these miRNAs were found to significantly suppress the growth and metastasis of PCa cells by negatively regulating the expression of MTDH. On the whole, the findings of this study demonstrate that MTDH functions as an oncogene in PCa and the inhibition of MTDH by miR­145­5p or miR­145­3p suppressed the growth and metastasis of PCa cells. The miR­145­5p/MTDH and miR­145­3p/MTDH pathways may thus become novel treatment targets for PCa.

Long noncoding RNA BDNF-AS is associated with clinical outcomes and has functional role in human prostate cancer.

BACKGROUND: The underlying molecular mechanisms of prostate cancer (CaP) are largely unknown. We investigated the expression, prognostic value and functional role of long non-coding RNA (lncRNA) brain-derived neurotrophin factor antisense (BDNF-AS) in CaP. METHODS: Clinical tumor samples were excised from patients with CaP. Their endogenous BDNF-AS expression levels were evaluated by qRT-PCR. Correlations between CaP patients' endogenous BDNF-AS expression and their clinicopathological factors, overall survival were statistically analyzed. BDNF-AS expression levels were also probed in immortal CaP cell lines. In LNCaP and PC-3 cells, BDNF-AS was ectopically overexpressed through lentiviral transduction. The functions of BDNF-AS upregulation on CaP cell development were evaluated both in vitro and in vivo. RESULTS: BDNF-AS was downregulated in human CaP tumors. Low BDNF-AS expression was correlated with CaP patients' poor prognosis and shorter overall survival. BDNF-AS was also found to be lowly expressed in CaP cell lines. In LNCaP and PC-3 cells, lentivirus-driven BDNF-AS overexpression exerted significantly tumor-suppressing effects on hindering cancer cell proliferation and invasion in vitro, and explant growth in vivo. CONCLUSION: Downregulated BDNF-AS in CaP patients could be a potential prognostic biomarker for predicating poor prognosis and survival. Upregulating BDNF-AS may be a novel molecular intervening target for CaP treatment.

miR-24-3p regulates bladder cancer cell proliferation, migration, invasion and autophagy by targeting DEDD.

microRNAs (miRNAs), a class of small non-coding RNA molecules, can regulate gene expression by interacting with the 3'-untranslated regions (3'UTR) of target genes and influence various biological processes. We investigated the potential role of miR-24-3p in the development of bladder cancer by regulating DEDD, a member of the death effector domain-containing protein family. First, we found that miR-24-3p was highly expressed and that DEDD was expressed at a low level in bladder cancer tissues compared with that in adjacent bladder tissues by qRT-PCR (P<0.0001). Second, we found that miR-24-3p promoted the proliferation ability of bladder cancer cells using the MTT assay and colony forming assay; and showed that miR-24-3p accelerated the migration and invasion of bladder cancer cells using migration and invasion assays (P<0.05). Moreover, miR-24-3p inhibited apoptosis of bladder cancer cells, as shown by flow cytometry (P<0.05). Western blot results demonstrated that miR-24-3p participated in autophagy of bladder cancer cells by DEDD. In addition, the tumor formation assay showed that miR-24-3p promoted the growth of bladder tumor in vivo. Furthermore, the luciferase reporter gene assay indicated that miR-24-3p suppressed DEDD gene transcription. Therefore, our study indicated that miR-24-3p promoted bladder cancer progression by inhibiting DEDD.

[Corrigendum] 5­bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2­one induces apoptosis in T24 human bladder cancer cells through mitochondria-dependent signaling pathways.

Following the publication of this article, an interested reader drew to our attention that Fig. 1, which described the effects of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on T24 bladder carcinoma cell morphology and viability, contained a pair of panels showing identical data. After having re-examined our original data, we realize that the control data (showing 0 µM BHP) were inadvertently also included in Fig. 1 for the panel that was intended to show the effect of adding 10 µM BHP to the cells. A corrected version of Fig. 1, featuring the correct data for the addition of 10 µM BHP to the cells, is shown here. The error did not affect the conclusions reported in this study. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the Molecular Medicine Reports 15: 153-159, 2016; DOI: 10.3892/mmr.2016.5991].

5­bromo­3­(3­hydroxyprop­1­ynyl)­2H­pyran­2­one induces apoptosis in T24 human bladder cancer cells through mitochondria-dependent signaling pathways.

The present study was performed to investigate the effect of 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) on the induction of apoptosis and cell cycle arrest in T24 human bladder carcinoma cells. An MTT assay was used to investigate the inhibition of cell proliferation. Flow cytometry was used to observe alterations in the cell cycle, generation of reactive oxygen species (ROS), alterations in mitochondrial membrane potential (MMP) and induction of apoptosis in the T24 cells following BHP treatment. Western blot analysis was performed for the determination of expression levels of apoptotic proteins, and 4,6­diamidino­2­phenylindole dihydrochloride staining was used to observe apoptosis and DNA damage. The results demonstrated that treatment of the bladder cancer cells with BHP enhanced the activation of caspases and increased the production of ROS. It also caused damage to DNA, reduced MMP, and increased the secretion of endonuclease G and apoptosis­inducing factor from the mitochondria. The expression levels of cyclin E and cell division cycle 25C were reduced, whereas the expression levels of p21 and phosphorylated p53 were increased in the BHP­treated cells. In addition, treatment with BHP caused cell cycle arrest at the G0/G1 phase, increased the expression levels of B cell lymphoma­2 (Bcl­2)­associated X protein and poly(ADP­ribose) polymerase, decreased the expression of Bcl­2 and ultimately induced apoptosis of the T24 cells. Thus, BHP inhibited the proliferation of bladder cancer cells by inducing cell apoptosis through the mitochondrial pathway.

Chk1 knockdown confers radiosensitization in prostate cancer stem cells.

Radioresistance is responsible for treatment failure after radiotherapy in localized prostate cancer, while prostate cancer stem cells promote radioresistance by preferential activation of the DNA damage response. Chk1 inhibition has been shown to sensitize many tumor cells to radiation. However, whether Chk1 inhibition can potentiate the cytotoxic effects of radiation on prostate cancer stem cells remains to be elucidated. In this study, CD133+CD44+ cells were isolated using microbeads and were found to possess cancer stem cell properties. Using shRNA, Chk1 was knocked down in the sorted CD133+CD44+ cells. Our results demonstrated that Chk1 knockdown abrogated the radiation-induced G2/M arrest, inhibited DNA damage repair and promoted premature mitosis, leading to increased apoptosis in the radiated sorted CD133+CD44+ cells. Moreover, these effects were accompanied by caspase-2 activation and the inactivation of phosphorylated Cdc25C and Cdc2. Our results suggest that Chk1 knockdown increases the radiosensitivity of CD133+CD44+ prostate cancer stem cells. Chk1 knockdown in prostate cancer stem cells may be an effective therapeutic strategy against prostate cancer.