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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]

[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]