Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present research focused on designing a quinazoline skeleton, framed via 1,3,5-triazine derivatives (QBT) through field mapping and alignment studies. The QBT derivatives were synthesized via time- and cost-effective protocol. The 3D-QSAR study, computational physicochemical properties, and ADME calculation of the derivatives were performed to establish the affinity towards the biological system. Molecular docking in the adenosine triphosphate binding site of the RET tyrosine kinase domain (PDB ID: 7IVU) was studied to elucidate vital structural residues necessary for bioactivity. The derivatives were evaluated for anticancer potency against TPC-1 cells (thyroid cancer), MCF-7 cells (breast cancer), and one normal cell line (human foreskin fibroblasts) via 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay followed by an in ovo CAM assay. The entire series of derivatives (8a-o) showed mild to significant anticancer potency against the selected cancer cell lines.
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PMID:Quinazoline based 1,3,5-triazine derivatives as cancer inhibitors by impeding the phosphorylated RET tyrosine kinase pathway: Design, synthesis, docking, and QSAR study. 3138 May 98

Papillary thyroid carcinoma (PTC) is recognized as one of the most prevalent types of thyroid cancer with poor prognosis. Long noncoding RNA (lncRNA) has undergone an intensive study for their involvement in tumor treatment. This study intends to unravel the association of lncRNA SLC26A4-AS1 with PTC. Initially, PTC-related expression profiling data (GSE33630) was utilized to screen differentially expressed lncRNAs in PTC and the underlying mechanisms involved with the mitogen-activated protein kinase (MAPK) pathway. Moreover, PTC tumor tissues and paracancerous tissues were arranged to determine expressions of TP53, SLC26A4-AS1, and genes related to epithelial-mesenchymal transition (EMT) and the MAPK pathway. Furthermore, SLC26A4-AS1 was overexpressed or underexpressed and JNK was underexpressed through cell transfection to examine the effect of SLC26A4-AS1 on PTC via MAPK pathway. Besides, tumor formation in nude mice was used to verify the fore experiment. LncRNA SLC26A4-AS1 regulating TP53 had the potential to participate in PTC by regulating the MAPK pathway. SLC26A4-AS1 was expressed poorly in PTC. Notably, SLC26A4-AS1 elevated E-cadherin expression while it reduced that of ERK and Vimentin. In addition, the overexpression of SLC26A4-AS1 inactivated the MAPK pathway by promoting TP53 and decreased cell migration, proliferation, and invasion. In addition to all these effects, the overexpression of SLC26A4-AS1 promoted apoptosis of TPC-1 cells. Additionally, the overexpression of lncRNA SLC26A4-AS1 reduced xenograft tumor volume in nude mice. Furthermore, the effect of SLC26A4-AS1 overexpression was found to be promoted after the MAPK pathway inactivation. Taken together, the overexpression of lncRNA SLC26A4-AS1 coffered anti-oncogenic effects on PTC through the inactivation of the MAPK pathway.
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PMID:Overexpression of long noncoding RNA SLC26A4-AS1 inhibits the epithelial-mesenchymal transition via the MAPK pathway in papillary thyroid carcinoma. 3155 16

Phenformin is a biguanide drug which, besides the original anti-diabetic effect, also exerts anti-cancer effects. The aim of this study was to further characterize these latter in terms of both cell-viability and modulation of the secretion of the pro-tumorigenic chemokine CXCL8. Normal human thyrocytes in primary cultures (NHT) and thyroid cancer cell lines, TPC-1 and 8505C (RET/PTC and BRAFV600E mutated, respectively) were treated with increasing concentrations of phenformin at different times. Cell-viability was assessed by WST-1 and further characterized by AnnexinV/PI staining and cell proliferation colony-assay. CXCL8 levels were measured in cell supernatants. Phenformin reduced cell-viability in TPC-1 and 8505C and their ability to form colonies. In NHT cells, phenformin affected cell-viability only at the maximal dose but interestingly it inhibited CXCL8 secretion at all the concentrations not affecting cell-viability. Phenformin had no effect on CXCL8 secretion in thyroid cancer cell lines. Thus, phenformin exerts anti-cancer effects on both cancer cells (cell death induction) and surrounding normal cells (inhibition of CXCL8 secretion). These results highlight that the anti-cancer effects of phenformin are multifaceted and effective on both solid and soluble components of the tumor-microenvironment.
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PMID:The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes. 3174 8

Papillary thyroid carcinoma (PTC) is the prevalent histotype of thyroid cancer, with increasing incidence worldwide. MicroRNAs (miRNAs) could play an important role in the development and progression of human cancers. Interestingly, miR-326 was validated as one of the downregulated miRNAs in PTC. Therefore, it is necessary to research the function of miR-326 involved in the progression of PTC. In the current study, we detected the downregulation of miR-326 in PTC tissues and cell lines. The miR-326 overexpression or knockdown was conducted in TPC-1 or HTh83 PTC cells. miR-326 mimics decreased the proliferation, clone formation ability and caused G1-phase accumulation. In addition, the reduction of migration and invasion abilities was induced by miR-326 mimics. Western blot analysis showed that the cells with miR-326 mimics exhibited the inhibition of vimentin and N-cadherin, as well as enhancement of E-cadherin. Importantly, miR-326 could directly target mitogen activated protein kinase 1 (MAPK1) and epidermal growth factor receptor 4 (ERBB4). MAPK1 or ERBB4 overexpression rescued the effects of miR-326 on proliferation, migration, and invasion in PTC cells. Notably, miR-326 reduced tumorigenesis in vivo, including the decrease of tumor volume and weight, suppression of Ki-67, N-cadherin, MAPK1 and ERBB4. In all, these results might provide a new therapeutic target for the diagnosis of PTC.
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PMID:miR-326 inhibits the progression of papillary thyroid carcinoma by targeting MAPK1 and ERBB4. 3226 16


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