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LncRNA-IMAT1 Promotes Invasion of Meningiomas by Suppressing KLF4/hsa-miR22-3p/Snai1 Pathway
Tao Zhang,Yu Ge,Daijun Wang,Qin Liu,Shuchen Sun,Lingyang Hua,Jiaojiao Deng,Shihai Luan,Haixia Cheng,Qing Xie,Ye Gong,Tao Zhang 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.6
Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.
Gong Haoli,Tao Ye,Xiao Sheng,Li Xin,Fang Ke,Wen Jie,He Pan,Zeng Ming 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Long noncoding RNAs (lncRNAs), widely expressed in mammalian cells, play pivotal roles in osteosarcoma (OS) progression. Nevertheless, the detailed molecular mechanisms of lncRNA KIAA0087 in OS remain obscure. Here, the roles of KIAA0087 in OS tumorigenesis were investigated. KIAA0087 and miR-411-3p levels were detected by RT-qPCR. Malignant properties were assessed by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. SOCS1, EMT, and JAK2/STAT3 pathway-related protein levels were measured by western blotting. Direct binding between miR-411-3p and KIAA0087/SOCS1 was validated by a dual-luciferase reporter, RIP, and FISH assays. In vivo growth and lung metastasis were evaluated in nude mice. The expression levels of SOCS1, Ki-67, E-cadherin, and N-cadherin in tumor tissues were measured by immunohistochemical staining. Downregulation of KIAA0087 and SOCS1 and upregulation of miR-411-3p were found in OS tissues and cells. Low expression of KIAA0087 was associated with a poor survival rate. Forced expression of KIAA0087 or miR-411-3p inhibition repressed the growth, migration, invasion, EMT, and activation of the JAK2/STAT3 pathway and triggered apoptosis of OS cells. However, the opposite results were found with KIAA0087 knockdown or miR-411-3p overexpression. Mechanistic experiments indicated that KIAA0087 enhanced SOCS1 expression to inactivate the JAK2/STAT3 pathway by sponging miR-411-3p. Rescue experiments revealed that the antitumor effects of KIAA0087 overexpression or miR-411-3p suppression were counteracted by miR-411-3p mimics or SOCS1 inhibition, respectively. Finally, in vivo tumor growth and lung metastasis were inhibited in KIAA0087-overexpressing or miR-411-3p-inhibited OS cells. In summary, the downregulation of KIAA0087 promotes the growth, metastasis, and EMT of OS by targeting the miR-411-3p-mediated SOCS1/JAK2/STAT3 pathway.
Gong Ting,Jia Bin,Gu Liyan,Yu Tao 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.1
Background A large number of clinical trials have proved that radiotherapy is an effective strategy for treating breast cancer (BC), but radioresistance is an urgent problem to be solved. Objective Herein, radio-tolerant BC cell lines named MDA-MB-231/R and MCF-7/R were successfully constructed, respectively, and it was shown that microRNA-125b-5p (miR-125b-5p) was lowly expressed in radio-tolerant cells, which was associated with poor prognosis of BC patients. Results Furthermore, miR-125b-5p over expression could hinder cell proliferation and strengthen radio-sensitivity. Mechanistically, Breast Cancer 1 (BRCA1) was identified as a downstream protein target of miR-125b-5p in BC cells, and Kruppellike factor 5 (KLF5) was identified as an upstream transcription factor involved in promoting miR-125b-5p expression. More importantly, over expression of KLF5 suppressed BC cell proliferation and increased its radiation sensitivity, which could be retained by miR-125b-5p downregulation. Conclusion In conclusion, these findings suggested that the KLF5/miR-125b-5p/BRCA1 axis may provide new information on radiation therapy for breast cancer.
Gong, Hai-Yang,Sun, Meng-Xiong,Hu, Shuo,Tao, Ying-Ying,Gao, Bo,Li, Guo-Dong,Cai, Zheng-Dong,Yao, Jian-Zhong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5
Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dosedependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.
Tao Zhang,Yong-zhi Gong,Fa-xing Ding,Xue-mei Liu,Zhi-wu Yu 국제구조공학회 2021 Structural Engineering and Mechanics, An Int'l Jou Vol.78 No.3
Pure bending loading conditions are not frequently occurred in practical engineering, but the flexural researches are important since it’s the basis of mechanical property researches under complex loading. Hence, the objective of this paper is to investigate the flexural behavior of concrete-filled rectangular steel tube (CFRT) through combined experimental and numerical studies. Flexural tests were conducted to investigate the mechanical performance of CFRT under bending. The load vs. deflection curves during the loading process was analyzed in detail. All the specimens behaved in a very ductile manner. Besides, based on the experimental result, the composite action between the steel tube and core concrete was studies and examined. Furthermore, the feasibility and accuracy of the numerical method was verified by comparing the computed results with experimental observations. The full curves analysis on the moment vs. curvature curves was further conducted, where the development of the stress and strain redistribution in the steel tube and core concrete was clarified comprehensively. It should be noted that there existed bond slip between the core concrete and steel tube during the loading process. And then, an extensive parametric study, including the steel strength, concrete strength, steel ratio and aspect ratio, was performed. Finally, design formula to calculate the ultimate moment and flexural stiffness of CFRTs were presented. The predicted results showed satisfactory agreement with the experimental and FE results. Additionally, the difference between the experimental/FE and predicted results using the related design codes were illustrated.