Tunable Fluorescence and Morphology of Aggregates Built from a Mechanically Bonded Amphiphilic Bistable [2]Rotaxane.

Advanced Organic Chemical Materials Co-constructed Mechanically bonded amphiphiles (MBAs), also known as mechanically interlocked molecules (MIMs), have emerged as an important kind of functional building block for the construction of artificial molecular machines and soft materials. Herein, a novel MBA, i. e., bistable [2]rotaxane H2 was designed and synthesized. In the solution state, H2 demonstrated pH and metal ion-responsive emissions due to the presence of a distance-dependent photoinduced electron transfer (PET) process and the fluorescence resonance energy transfer (FRET) process, respectively. Importantly, the amphiphilic feature of H2 has endowed it with unique self-assembly capability, and nanospheres were obtained in a mixed H2 O/CH3 CN solvent. Moreover, the morphology of H2 aggregates can be tuned from nanospheres to vesicles due to the pH-controlled shuttling motion-induced alternation of H2 amphiphilicity. Interestingly, larger spheres with novel pearl-chain-like structures from H2 were observed after adding stoichiometric Zn2+ . In particular, H2 shows pH-responsive emissions in its aggregation state, allowing the visualization of the shuttling movement by just naked eyes. It is assumed that the well-designed [2]rotaxane, and particularly the proposed concept of MBA shown here, will further enrich the families of MIMs, offering prospects for synthesizing more MIMs with novel assembly capabilities and bottom-up building dynamic smart materials with unprecedented functions.

Methyltransferase SETD2 inhibits tumor growth and metastasis via STAT1-IL-8 signaling-mediated epithelial-mesenchymal transition in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a major subtype of non-small-cell lung cancer, which is the leading cause of cancer death worldwide. The histone H3K36 methyltransferase SETD2 has been reported to be frequently mutated or deleted in types of human cancer. However, the functions of SETD2 in tumor growth and metastasis in LUAD has not been well illustrated. Here, we found that SETD2 was significantly downregulated in human lung cancer and greatly impaired proliferation, migration, and invasion in vitro and in vivo. Furthermore, we found that SETD2 overexpression significantly attenuated the epithelial-mesenchymal transition (EMT) of LUAD cells. RNA-seq analysis identified differentially expressed transcripts that showed an elevated level of interleukin 8 (IL-8) in STED2-knockdown LUAD cells, which was further verified using qPCR, western blot, and promoter luciferase report assay. Mechanically, SETD2-mediated H3K36me3 prevented assembly of Stat1 on the IL-8 promoter and contributed to the inhibition of tumorigenesis in LUAD. Our findings highlight the suppressive role of SETD2/H3K36me3 in cell proliferation, migration, invasion, and EMT during LUAD carcinogenesis, via regulation of the STAT1-IL-8 signaling pathway. Therefore, our studies on the molecular mechanism of SETD2 will advance our understanding of epigenetic dysregulation at LUAD progression.