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Precise regulation of protein activity and localization in cancer cells is crucial to dissect the function of the protein‐involved cellular network in tumorigenesis, but there is a lack of suitable methodology. Here we report the design of enzyme‐operated spherical nucleic acids (E‐SNAs) for manipulation of the nucleocytoplasmic translocation of proteins with cancer‐cell selectivity. The E‐SNAs are constructed by programmable engineering of aptamer‐based modules bearing enzyme‐responsive units in predesigned sites and further combination with SNA nanotechnology. We demonstrate that E‐SNAs are able to regulate cytoplasmic‐to‐nuclear shuttling of RelA protein efficiently and specifically in tumor cells, while they remain inactive in normal cells due to insufficient enzyme expression. We further confirmed the generality of this strategy by investigating the enzyme‐modulated inhibition/activation of thrombin activity by varying the aptamer‐based design. [ABSTRACT FROM AUTHOR]

MYC oncogene is involved in the majority of human cancers and is often associated with poor outcomes, rendering it an extraordinarily desirable target, but therapeutic targeting of c‐Myc protein has been a challenge for >30 years. Here, WBC100, a novel oral active molecule glue that selectively degrades c‐Myc protein over other proteins and potently kills c‐Myc overexpressing cancer cells is reported. WBC100 targets the nuclear localization signal 1 (NLS1)–Basic–nuclear localization signal 2 (NLS2) region of c‐Myc and induces c‐Myc protein degradation through ubiquitin E3 ligase CHIP mediated 26S proteasome pathway, leading to apoptosis of cancer cells. In vivo, WBC100 potently regresses multiple lethal c‐Myc overexpressing tumors such as acute myeloid leukemia, pancreatic, and gastric cancers with good tolerability in multiple xenograft mouse models. Identification of the NLS1–Basic–NLS2 region as a druggable pocket for targeting the "undruggable" c‐Myc protein and that single‐agent WBC100 potently regresses c‐Myc overexpressing tumors through selective c‐Myc proteolysis opens new perspectives for pharmacologically intervening c‐Myc in human cancers. [ABSTRACT FROM AUTHOR]

aims to explore whether miR-195-5p can inhibit proliferation and induce apoptosis of non-small cell lung cancer (NSCLC) cells by targeting CEP55. Methods: qRT-PCR was used to measure the expression of miR-195-5p in NSCLC cells. MTT assay, colony formation assay, and flow cytometry were used to detect the role of miR-195-5p in NSCLC cells. Western blot was used to measure the protein expression of CEP55, Bax and Bcl-2 in cells. Dual-Luciferase assay was performed to verify the relationship between miR-195-5p and CEP55. Results: The expression of miR-195-5p was higher in human normal lung cell lines than in NSCLC cells. MiR-195-5p overexpression inhibited cell proliferation, which could block the cell cycle of A549 cell line in the G0/G1 phase. Moreover, overexpression of miR-195-5p increased cell apoptotic rate of A549 cell lines, with the expression of pro-apoptotic protein Bax up-regulated and that of the anti-apoptotic protein Bcl-2 down-regulated. The Dual-Luciferase assay showed that miR-195-5p could specifically target CEP55. Furthermore, CEP55 was down-regulated in NSCLC cells. Overexpression of CEP55 enhanced the proliferation and colony formation ability of A549 cell line. Overexpression of CEP55 can reverse the inhibitory effect of miR-195-5p. Conclusion: MiR-195-5p inhibits proliferation and induces apoptosis of NSCLC cells by negatively regulating CEP55. [ABSTRACT FROM AUTHOR]

Abstract Background Propofol is a popular anesthetic agent, with potent anti-tumor activity against many cancers. The objective of this study was to explore the potential effect of propofol on papillary thyroid cancer (PTC) in vitro. Methods Human PTC cell lines TPC-1 and IHH-4 were treated by propofol. ANRIL expression vector (pc-ANRIL) was transfected into TPC-1 cells to overexpress the expression of ANRIL. CCK-8, BrdU assay, transwell assay, flow cytometry and Western blot were performed to evaluate cell proliferation, migration and apoptosis. The expression changes of ANRIL were detected by RT-qPCR. Results Propofol with a concentration of 6 μg/mL significantly reduced TPC-1 and IHH-4 cells proliferation and migration, and significantly induced apoptosis. However, 6 μg/mL of propofol had no significant impacts on the proliferation and apoptosis of normal human thyroid follicular epithelial Nthy-ori 3–1 cells. Meanwhile, the expression of ANRIL in TPC-1 cells was down-regulated by propofol. The anti-tumor activity of propofol was attenuated when ANRIL was overexpressed. Additionally, propofol blocked Wnt/β-catenin and NF-κB pathways in an ANRIL-dependent fashion. Conclusion Our findings suggested the in vitro anti-tumor potential of propofol in PTC. One possible mechanism involved in the anti-tumor activity was preliminary revealed: propofol down-regulated the expression of ANRIL, and thus blocking Wnt/β-catenin and NF-κB pathways. Highlights • Propofol suppresses PTC cells proliferation and migration. • Propofol induces PTC cells apoptosis. • Propofol down-regulates ANRIL expression. • Propofol blocks Wnt/β-catenin and NF-κB pathways. • Propofol confers its action via down-regulation of ANRIL. [ABSTRACT FROM AUTHOR]

Cancer Cell Specificity, Enzymes, Protein Function Regulation, Spherical Nucleic Acids, Subcellular Translocation The system enables enzyme-activated capture of proteins of interest and thus regulation of their cytoplasmic-nuclear shuttling with tumor-cell specificity, as reported by Mengyuan Li and co-workers in their Research Article (e202214958). Keywords: Cancer Cell Specificity; Enzymes; Protein Function Regulation; Spherical Nucleic Acids; Subcellular Translocation EN Cancer Cell Specificity Enzymes Protein Function Regulation Spherical Nucleic Acids Subcellular Translocation 1 1 1 04/18/23 20230424 NES 230424 B Cell-selective regulation b of protein translocation is achieved through the rational design of an endogenous enzyme-operated spherical nucleic acids platform. [Extracted from the article]

It has been reported that microRNAs (miRs) contribute to several biological functions and are associated with drug resistance in various types of cancer. However, to the best of our knowledge, whether miR-613 can affect cisplatin (CDDP) sensitivity in non-small cell lung cancer (NSCLC) remains unknown. Reverse transcription-quantitative PCR was performed to detect the expression levels of miR-613 and gap junction α-1 protein (GJA1) in patients with NSCLC. Cell Counting Kit-8, colony formation and Transwell assays were employed to exam the effects of miR-613 and GJA1 on cell functions. Cell apoptosis was analyzed using flow cytometry. An in vivo experiment was conducted to determine the influence of miR-613 on tumor formation. In the present study, miR-613 was revealed to be significantly downregulated in lung cancer tissues compared with in adjacent normal tissues, and low miR-613 expression indicated a poor prognosis. Furthermore, cell proliferation, colony formation and migration of lung cancer cells were inhibited by overexpression of miR-613. In vivo experiments also demonstrated that miR-613 could inhibit tumor growth. Moreover, miR-613 could enhance the negative effects of CDDP on cell proliferation, apoptosis and migration. GJA1 was revealed to be a target gene of miR-613 and was upregulated in human lung cancer tissues. Rescue experiments demonstrated that miR-613 increased the chemosensitivity of lung cancer cells by targeting GJA1. Collectively, the results suggested a tumor suppressor role of miR-613 in NSCLC and indicated that miR-613 could strengthen CDDP sensitivity in NSCLC cells by targeting GJA1, which may provide a novel therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]