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Advancement in our current understanding of miRNAs is essential to discover new and effective biomarkers for diagnostic, prognostic, and therapeutic goals of cancer patients.

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment. Under the guidance of cytotoxic activity, crude extracts of 55 fungal strains from the medicinal mangrove Acanthus ilicifolius were evaluated, and one potent cytotoxic natural compound, brefeldin A (BFA), was discovered from Penicillium sp. (HS-N-29).

This study was aimed to determine the cytotoxic activity of BFA and the effect on the activation and expression of BCR-ABL in K562 cells.

We evaluated cytotoxic activity by MTT assay and soft agar clone assay and apoptosis and cell cycle distribution by Muse cell analyzer. The protein level of BCR-ABL and signaling molecules were detected by western blotting, and the mRNA level of BCR-ABL was determined by RT-PCR.

BFA inhibited cell proliferation, induced G2/M cell cycle arrest, and stimulated cell apoptosis in K562 cells. Importantly, for the first time, we revealed that BFA inhibited the activation of BCR-ABL and consequently inhibited the activation of its downstream signaling molecules in K562 cells. Moreover, we found that BFA degraded BCR-ABL without affecting its transcription in K562 cells, and BFA-induced BCR-ABL degradation was related to caspase activation while not to autophagy or ubiquitinated proteasome degradation pathway.

Our present results indicate that BFA acts as a dual functional inhibitor and degrader of BCR-ABL, and BFA is a potential compound for chemotherapeutics to overcome CML.

Our present results indicate that BFA acts as a dual functional inhibitor and degrader of BCR-ABL, and BFA is a potential compound for chemotherapeutics to overcome CML.DNA integrity is continuously challenged by intrinsic cellular processes and environmental agents. To overcome this genomic damage, cells have developed multiple signaling pathways collectively named as DNA damage response (DDR) and composed of three components (i) sensor proteins, which detect DNA damage, (ii) mediators that relay the signal downstream and recruit the repair machinery, and (iii) the repair proteins, which restore the damaged DNA. A flawed DDR and failure to repair the damage lead to the accumulation of genetic lesions and increased genomic instability, which is recognized as a hallmark of cancer. Cancer cells tend to harbor increased mutations in DDR genes and often have fewer DDR pathways than normal cells. This makes cancer cells more dependent on particular DDR pathways and thus become more susceptible to compounds inhibiting those pathways compared to normal cells, which have all the DDR pathways intact. Understanding the roles of different DDR proteins in the DNA damage response and repair pathways and identification of their structures have paved the way for the development of their inhibitors as targeted cancer therapy. In this review, we describe the major participants of various DDR pathways, their significance in carcinogenesis, and focus on the inhibitors developed against several key DDR proteins.

Colony-stimulating factor-1 (CSF1) is a cytokine that is closely related to normal organ growth and development as well as tumor progression.

We aimed to summarize and clarify the reasons for the abnormal expression of CSF1 in tumors and explore the role of CSF1 in tumor progression. Furthermore, drug response analysis may provide a reference for clinical medication.

The expression of CSF1 was analyzed by TCGA and CCLE. Besides, cBioPortal and MethSurv databases were used to conduct mutation and DNA methylation analyses. Further, correlations between CSF1 expression and tumor stage, survival, immune infiltration, drug sensitivity and enrichment analyses were validated via UALCAN, Kaplan-Meier plotter, TIMER, CTRP and Coexperia databases.

CSF1 is expressed in a variety of tissues, meaningfully, it can be detected in blood. Compared with normal tissues, CSF1 expression was significantly decreased in most tumors. selleck chemicals llc The missense mutation and DNA methylation of CSF1 may cause the downregulated expression. Moreover, decreased CSF1 expression was related with higher tumor stage and worse survival. Further, the promoter DNA methylation level of CSF1 was prognostically significant in most tumors. Besides, CSF1 was closely related to immune infiltration, especially macrophages. Importantly, CSF1 expression was associated with a good response to VEGFRs inhibitors, which may be due to the possible involvement of CSF1 in tumor angiogenesis and metastasis processes.

The abnormal expression of CSF1 could serve as a promising biomarker of tumor progression and prognosis in pan-cancer. Significantly, angiogenesis and metastasis inhibitors may show a good response to CSF1-related tumors.

The abnormal expression of CSF1 could serve as a promising biomarker of tumor progression and prognosis in pan-cancer. Significantly, angiogenesis and metastasis inhibitors may show a good response to CSF1-related tumors.

New potential biological targets prediction through inverse molecular docking technique is an another smart strategy to forecast the possibility of compounds being biologically active against various target receptors.

In this case of designed study, we screened our recently obtained novel acetylinic steroidal biotransformed products [(1) 8-β-methyl-14-α-hydroxy∆4tibolone (2) 9-α-Hydroxy∆4 tibolone (3) 8-β-methyl-11-β-hydroxy∆4tibolone (4) 6-β-hydroxy∆4tibolone, (5) 6-β-9-α-dihydroxy∆4tibolone (6) 7-β-hydroxy∆4tibolone) ] from fungi Cunninghemella Blakesleana to predict their possible biological targets and profiling of ADME properties.

The prediction of pharmacokinetics properties membrane permeability as well as bioavailability radar properties were carried out by using Swiss target prediction, and Swiss ADME tools, respectively these metabolites were also subjected to predict the possible mechanism of action along with associated biological network pathways by using Reactome data-base.

All the six screened compounds possess excellent drug ability criteria, and exhibited exceptionally excellent non inhibitory potential against all five isozymes of CYP450 enzyme complex, including (CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4) respectively.