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Various biosensors based on aptamers are currently the most popular rapid detection approaches, but the performance of these sensors is closely related to the affinity of aptamers. In this work, a strategy for constructed high-affinity aptamer was proposed. By truncating the bases flanking the 59 nt dexamethasones (DEX) original aptamer sequence to improve the sensitivity of the aptamer to DEX, and then base mutation was introduced to further improve the sensitivity and selectivity of aptamers. Finally, the 33 nt aptamer Apt-M13 with G-quadruplex structures was obtained. The dissociation constant (Kd) was determined to be 200 nM by Graphene oxide (GO)-based fluorometry. As-prepared Apt-M13 was used for a label-free colorimetric aptamer sensor based on gold nanoparticles, the LOD was 3.2-fold lower than the original aptamer described in previous works. The anti-interference ability of DEX analogs is also further improved. It indicates that truncation technology effectively improves the specificity of the aptamer to DEX in this work, and the introduction of mutation further improves the affinity and selectivity of the aptamer to DEX. Therefore, the proposed aptamer optimization method is also expected to become a general strategy for various aptamer sequences.

Feifei Pu,1,* Fengxia Chen,2,* Jianxiang Liu,1 Zhicai Zhang,1 Zengwu Shao1 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zengwu ShaoDepartment of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, People’s Republic of ChinaTel/Fax +86 27 85351626Email 1985XH0536@hust.edu.cnAbstract: As a DNA receptor in the cytoplasm, cyclic GMP-AMP synthase (cGAS) contributes to the recognition of abnormal DNA in the cytoplasm and contributes to the stimulator of interferon genes (STING) signaling pathway. cGAS could mediate the expression of interferon-related genes, inflammatory-related factors, and downstream chemokines, thus initiating the immune response. The STING protein is a key effector downstream of the DNA receptor pathway. It is widely expressed across cell types such as immune cells, tumor cells, and stromal cells and plays a role in signal transduction for cytoplasmic DNA sensing and immunity. STING agonists, as novel agonists, are used in preclinical research and in the treatment of various tumors via clinical trials and have displayed attractive application prospects. Studying the cGAS-STING signaling pathway will deepen our understanding of tumor immunity and provide a basis for the research and development of antitumor drugs.Keywords: cGAS, STING, innate immunity, tumor, immunotherapy, drug discovery

Feifei Pu,1,* Fengxia Chen,2,* Zhicai Zhang,1 Jianxiang Liu,1 Zengwu Shao1 1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this work.Correspondence: Zengwu Shao Email 1985XH0536@hust.edu.cnAbstract: Osteosarcoma is a highly invasive kind of malignant bone tumor. Exosomes are a type of extracellular vesicles that play an important role in intercellular communication in the microenvironment. Tumor cell progression is promoted through the interaction between exosomes and cells in the microenvironment (including immune cells, mesenchymal cells, and endothelial cells) during tumor development. Neoplastic exosomes can carry a variety of biological information molecules, such as proteins, lipids, and nucleic acids. These molecules play an important clinical role, not only being able domesticate the recipient cells but also being recognized as tumor specific markers. At the same time, exosomes secreted by osteosarcoma can also cooperate with antigen-presenting cells to activate the body’s immune response and then to exert anti-tumor effects. Studies on exosomes may be a breakthrough in the search for a new osteosarcoma treatment. In this study, we review the role of neoplastic exosomes in the osteosarcoma microenvironment, summarize their potential as tumor markers, and investigate their clinical application prospects.Keywords: osteosarcoma, exosome, diagnosis, treatment, drug carrier, antitumor drug

Yan Dou,1 Fengxia Chen,1 Yawan Lu,1 Huanhuan Qiu,1 Hongmei Zhang2 1Department of Oncology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 2Department of Nursing, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of ChinaCorrespondence: Hongmei ZhangDepartment of Nursing, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of ChinaTel +86 371-65580952Email Z126hm@126.comObjective: This study aimed to investigate the effect of Wnt/β-catenin signal pathway mediated by miR-342-5p targeting CBX2 gene on the proliferation, metastasis, invasion and apoptosis of ovarian cancer cells, and to explore its related regulatory mechanism.Methods: Human normal ovarian epithelial cell line IOSE80, human ovarian cancer cell line SKOV3 and OVCAR3 were the subjects. Software were used to predict the binding site of miR-342-5p targeting CBX2 gene. The proliferation rate of ovarian cancer cells was detected by MTT method; the cell viability of each group was observed by colony formation test; the apoptosis of cells in each group was detected by flow cytometry; the invasive ability of cells was determined by transwell test, and the migration ability of cells was detected by scratch test. The mRNA expression levels of miR-342-5p, CBX2, Wnt1, β-catenin, C-myc and Cyclin D1 were measured by qRT-PCR. Also, Western blot was used to determine the protein expression levels of CBX2, Wnt1, β-catenin, C-myc and Cyclin D1.Results: CBX2 was identified as the target gene of miR-342-5p. MTT test results showed that miR-342-5p could significantly inhibit the proliferation of SKOV3 and OVCAR3 cells, colony formation assay results indicated that the viability of SKOV3 and OVCAR3 cells transfected with miR-342-5p decreased significantly, and flow cytometry results suggested that miR-342-5p could promote the apoptosis of SKOV3 and OVCAR3 cells. Also, the results of transwell showed that miR-342-5p could significantly inhibit the invasive ability of SKOV3 and OVCAR3 cells, and the results of scratch assay suggested that miR-342-5p could significantly inhibit the migration of SKOV3 and OVCAR3 cells. Moreover, qRT-PCR and Western blot results indicated that the mRNA and protein expression levels of CBX2, Wnt1, β-catenin, C-myc and Cyclin D1 decreased in SKOV3 and OVCAR3 cells transfected with miR-342-5p, while the mRNA expression levels of miR-342-5p increased significantly (P< 0.05).Conclusion: MiR-342-5p targeted gene is CBX2, which can significantly reduce the proliferation, invasion, migration and viability of ovarian cancer cell lines SKOV3 and OVCAR3, and promote their apoptosis. The mechanism may be related to the mediation of Wnt/β-catenin signal pathway and down-regulation of the related genes expression.Keywords: miR-342-5p, CBX2, ovarian cancer, Wnt/β-catenin signal pathway