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Prostate cancer is one of the most common cancers in men. This study was conducted to investigate the role of euchromatic histone lysine methyltransferase 2 (EHMT2) and endoplasmic reticulum protein 29 (ERP29) in the progression of radioresistance in prostate cancer. The expression of EHMT2 and ERP29 in prostate cancer cells and during the progression of radioresistance was detected using quantitative reverse transcription‐polymerase chain reaction and western blotting, and the interaction between EHMT2 and ERP29 was investigated. The proliferation of transfected cells under x‐ray irradiation was determined using the methyl thiazolyl tetrazolium and colony formation assays. Flow cytometry was used to analyze the apoptosis of the transfected cells under x‐ray irradiation. Nude mice were subcutaneously injected with prostate cancer (DU145) cells stably transfected with sh‐ERP29 or sh‐NC. The effect of ERP29 expression on radioresistance in nude mice was assessed by x‐ray irradiation. The expression of EHMT2 was upregulated and that of ERP29 was downregulated in prostate cancer cells during radioresistance progression. EHMT2 downregulation suppressed radioresistance in DU145 and androgen‐sensitive prostate cancer (LNCaP) cells. In irradiated DU145 cells, EHMT2 inhibition decreased the number of colonies and accelerated apoptosis. The transcription of ERP29 was suppressed by EHMT2 by upregulating H3K9me2 and downregulating H3K4me3, thereby regulating radioresistance in prostate cancer cells. In addition, the downregulation of ERP29 promoted the progression of radioresistance in prostate cancer cells in nude mice. EHMT2 promotes radioresistance in prostate cancer cells by repressing ERP29 transcription. [ABSTRACT FROM AUTHOR]

Mitochondria have a crucial role in regulating energy metabolism and their dysfunction has been linked to tumorigenesis. Cancer diagnosis and intervention have a great interest in the development of new agents that target biomolecules within mitochondria. However, monitoring and modulating mitochondria RNA (mtRNA), an essential component in mitochondria, in cells is challenging due to limited functional research and the absence of targeting agents. In this study, we designed and synthesized a fluorescent quinolinium derivative, QUCO-1, which actively lit up with mtRNA in both normal and cancer cells in vitro. Additionally, we evaluated the function of QUCO-1 as an mtRNA ligand and found that it effectively induced severe mitochondrial dysfunction and OXPHOS inhibition in RKO colorectal cancer cells. Treatment with QUCO-1 resulted in apoptosis, cell cycle blockage at the G2/M phase, and the effective inhibition of cell proliferation. Our findings suggest that QUCO-1 has great potential as a promising probe and therapeutic agent for mtRNA, with the potential for treating colorectal cancer. [ABSTRACT FROM AUTHOR]

Circular RNAs play critical roles in tumorigenesis. hsa_circ_0079480 was reported to be upregulated in colorectal cancer (CRC). However, its specific molecule in CRC is poorly understood. Hsa_circ_0079480, miR‐498, and ATP5E expressions in CRC tissues and CRC cells were determined using quantitative real‐time polymerase chain reaction assay. ATP5E protein level was assessed using Western blot. Cell proliferation, migration, and invasion were examined by 3‐(4, 5‐Dimethylthiazolyl2)‐2, 5‐diphenyltetrazolium bromide assay and Transwell assays, respectively. Dual‐luciferase reporter gene assay was performed to analyze the interactions between hsa_circ_0079480, miR‐498, and ATP5E. This study results showed that hsa_circ_0079480 and ATP5E expressions were significantly increased in CRC tissues and CRC cells, while miR‐498 was downregulated. Hsa_circ_0079480 knockdown dramatically suppressed CRC cell proliferation, migration, and invasion. Meanwhile, it turned out that hsa_circ_0079480 knockdown inhibited CRC tumor growth in vivo. Hsa_circ_0079480 could negatively regulate miR‐498 expression by directly targeting miR‐498. MiR‐498 overexpression dramatically inhibited CRC cell malignant behaviors. miR‐498 negatively regulated ATP5E expression by directly binding to ATP5E. ATP5E knockdown suppressed CRC cell malignant behaviors. ATP5E overexpression mitigated the inhibitory effect of hsa_circ_0079480 on CRC cell malignant behaviors. Since hsa_circ_0079480 knockdown inhibited CRC cells malignant behaviors through regulation of the miR‐498/ATP5E axis, it can be concluded that hsa_circ_0079480 might have great potential as therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

A novel series of cyclin-dependent kinases (CDKs) inhibitors, which play critical roles in the cell cycle control and regulation of cell transcription, were synthesised. A systematic study of enzymatic and cellular assays led to the identification of compound X22 with a nanomolar potency against CDK4 and CDK9 and potent antiproliferative activities against a panel of tumour cell lines. X22 could induce cell cycle arrest and cell apoptosis in cancer cell lines. X22 dose-dependently inhibits signalling pathways downstream of CDKs in cancer cells. In vivo antitumor activity assays, oral administration of X22 led to significant tumour regression in mouse model without obvious toxicity. Superior anti-cancer efficacy in vitro and in vivo of X22 demonstrated combined depletion of cell cycle and transcriptional CDK all contributed to antitumor activity. Taken together, concomitant inhibition of cell cycle and transcriptional CDK activities provided valuable guide for further structural optimisation. [ABSTRACT FROM AUTHOR]

Didymin is a dietary flavonoid that first found in citrus fruits, and possesses antioxidant properties. Our preliminary experiments first discovered that didymin was able to sensitize the resistant cancer cells against chemotherapeutics and combat multidrug resistance. However, its poor aqueous solubility and resultant low bioavailability limit its potentials as an adjuvant phytochemical drug for chemotherapy. Thus, this study prepared the inclusion complex of didymin with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin to improve its bioavailability and then evaluate their chemosensitization effects. The didymin inclusion complexes formulation was prepared and their host-guest structure was characterized by FT-IR, PXRD, DSC, and SEM techniques. In vitro/in vivo results demonstrated that didymin inclusion complex enhanced its water solubility and orally bioavailability. Furthermore, didymin inclusion complex exerted considerable chemosensitivity potency, and improve the anti-tumor effects of chemotherapeutics in vivo. Therefore, didymin inclusion complex could provide a safe, effective, economical, and adjuvant drug for future treatment of chemoresistant cancers. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are known to be important in a variety of cancer types. The specific expression and roles of miR-520f-3p in the context of gastric cancer (GC), however, remains unknown. Herein we determined miR-520f-3p expression to be significantly reduced in human GC cells compared to cells of the gastric epithelium, with comparable down-regulation also being evident in gastric cancer tissue samples and the low expression of this miRNA was positively correlated with features of more aggressive large tumor size (p = 0.019), depth of invasion (p = 0.008), and distant metastasis (p = 0.037). We further found that lower levels of miR-520f-3p corresponded with poorer GC patient overall (p = 0.003) and disease-free (p = 0.036) survival. When over-expressed in GC cells, miR-520f-3p was able to impair their growth, proliferation, and survival, instead leading to the induction of apoptosis. We further found that miR-520f-3p was able to bind the SOX9 3′-UTR, thereby negatively regulating its expression in GC cells. Consistent with this model, SOX9 and miR-520f-3p expression were negatively correlated with one another in GC tissues. When SOX9 was upregulated, this was also able to abrogate miR-520f-3p-mediated inactivation of Wnt/β-catenin signaling. Together our findings thus suggest that miR-520f-3p can act to suppress GC progression, at least in part via suppressing SOX9 expression and thus disrupting Wnt/β-catenin signaling. Our results thus highlight potential novel therapeutic targets in GC worthy of future investigation. [ABSTRACT FROM AUTHOR]

Background： Aloe-emodin, an anthraquinone present in aloe latex, has been shown to have anti-proliferative properties in cervical cancer disease, all cases of which are almost caused by human papillomavirus (HPV), with the products of E6/E7. It is suggested that aloe-emodin may play an important role in HPV-induced cervical cancer cells. Methods： Hela and SiHa cells were treated with various concentrations of aloe-emodin. MTT assay and flow cytometry were used to identify the cell growth and apoptosis. The expressions of HPV E6, E7 and GLUT1 (glucose transporter-1) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB). The glucose uptake, lactate production and ATP production in HeLa and SiHa cells were also investigated. Result： The results indicate that aloe-emodin promoted the apoptosis of HeLa and SiHa cells and decreased the expressions of HPV-related protein E6 and E7. Furthermore, aloe-emodin inhibited glucose metabolism by reducing GLUT1 expression. Overexpression of GLUT1 significantly weakened the apoptosis induced by aloe-emodin in HeLa cells. Conclusion： In this study, we found that aloe-emodin induce apoptosis of cervical cancer cells, which was associated with HPV E6 and E7 and glucose metabolism. [ABSTRACT FROM AUTHOR]

Background/Aims: Current practical advances in high-throughput data technologies including RNA-sequencing have led to the identification of long non-coding RNAs (lncRNAs) for potential clinical application against bladder urothelial cancer (BLCA). However, most previous studies focused on the clinical value of individual lncRNAs, which has limited the potential for future clinical application. Methods: In this study, RNA-sequencing data of lncRNAs was downloaded from The Cancer Genome Atlas database. Risk score was constructed based on survival-associated lncRNAs identified using differential expression analysis as well as univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic and Kaplan-Meier curve analyses were employed to evaluate the clinical and prognostic value of risk scores. Bioinformatics analyses were used to investigate the potential mechanisms of newly identified lncRNAs. Results: Among 2,127 differentially expressed lncRNAs (DELs), four new lncRNAs (AC145124.1, AC010168.2, MIR200CHG, and AC098613.1) showed valuable prognostic effects in BLCA patients. More importantly, the four-DEL-based risk score had the potential to become an independent marker for the survival status prediction of BLCA patients. Distinct co-expressed genes and signaling pathways were identified when BLCA was categorized into low- and high-risk groups. Furthermore, a protein-coding gene, HIST4H4 was found only 68 bp from the AC010168.2 DEL. HIST4H4 expression level was evidently up-regulated and positively correlated with AC010168.2 in BLCA patients. Conclusion: This in silico investigation pioneers the future investigation of the utility of prognostic lncRNAs for BLCA. [ABSTRACT FROM AUTHOR]

Introduction: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited. Materials and methods: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot. Result: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P,0.001). DNM3 downregulated the protein expression of MMP-2 and MMP-9. Conclusion: DNM3 may weaken the malignant behavior of colon cancer and may have promoted the invasion and migration of colon cancer by regulating the expression of MMP-2 and MMP-9. [ABSTRACT FROM AUTHOR]

The present study was carried out to investigate the potential of cationic functionalization on imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion of cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2) were prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential, and relatively high drug content with the aid of the polydopamine-coating technique. Efficient interaction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related to the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution on mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis induction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over unmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in Pluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature and sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2 exhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal residence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model tumors indicated by smaller tumor size, longer median survival time, and more intratumor apoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed NC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer via intravaginal administration. [ABSTRACT FROM AUTHOR]

[Display omitted] • Various acridone derivatives were synthesized and evaluated for anticancer activity. • C4 exhibited potent activity against Hep-G2 cells with IC 50 value of 6.29 ± 0.93 μM. • C4 could specifically bind to and destabilize Kras gene promoter i-motif structure. • C4 down-regulated Kras gene expression possibly through its promoter i-motif. • C4 induced cell apoptosis possibly related to its effect on mitochondrial dysfunction. Two series of novel acridone derivatives were designed and synthesized, with their anticancer activity evaluated. Most of these compounds showed potent antiproliferative activity against cancer cell lines. Among them, compound C4 with dual 1,2,3-triazol moieties exhibited the most potent activity against Hep-G2 cells with IC 50 value determined to be 6.29 ± 0.93 μM. Subsequent experiments showed that C4 could bind to and destabilize Kras gene promoter i-motif structure without significant interaction with its corresponding G-quadruplex. C4 could down-regulate Kras expression in Hep-G2 cells, possibly due to its interaction with the Kras i-motif. Further cellular studies indicated that C4 could induce apoptosis of Hep-G2 cells, possibly related to its effect on mitochondrial dysfunction. These results indicated that C4 could be further developed as a promising anticancer agent. [ABSTRACT FROM AUTHOR]

Summary: Glioblastomas display cellular hierarchies containing tumor-propagating glioblastoma stem cells (GSCs). STAT3 is a critical signaling node in GSC maintenance but molecular mechanisms underlying STAT3 activation in GSCs are poorly defined. Here we demonstrate that the bone marrow X-linked (BMX) nonreceptor tyrosine kinase activates STAT3 signaling to maintain self-renewal and tumorigenic potential of GSCs. BMX is differentially expressed in GSCs relative to nonstem cancer cells and neural progenitors. BMX knockdown potently inhibited STAT3 activation, expression of GSC transcription factors, and growth of GSC-derived intracranial tumors. Constitutively active STAT3 rescued the effects of BMX downregulation, supporting that BMX signals through STAT3 in GSCs. These data demonstrate that BMX represents a GSC therapeutic target and reinforces the importance of STAT3 signaling in stem-like cancer phenotypes. [ABSTRACT FROM AUTHOR]

Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in metastatic tumors. Periostin expression dramatically enhanced metastatic growth of colon cancer by both preventing stress-induced apoptosis in the cancer cells and augmenting endothelial cell survival to promote angiogenesis. At the molecular level, periostin activated the Akt/PKB signaling pathway through the αvβ3 integrins to increase cellular survival. These data demonstrated that the survival-promoting function is crucial for periostin to promote tumor metastasis of colon cancer. [Copyright &y& Elsevier]