Abstract. 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 domaincontaining 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.
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.
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-AS1mediated 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.
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 RT-qPCR, 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, RT-qPCR, western blot analysis, dual-luciferase reporter assay and MTT assay were performed to identify direct the target of MTDH and to examine tumor cell viability. Rescue experiments using the PC-3 and LNCaP cells were carried out by MTT assay, scratch wound assay, Transwell assay, RT-qPCR 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. miR-145-5p and miR-145-3p 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 miR-145-5p or miR-145-3p suppressed the growth and metastasis of PCa cells. The miR-145-5p/MTDH and miR-145-3p/MTDH pathways may thus become novel treatment targets for PCa.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.