Journal of Biomaterials and Tissue Engineering
·
2018
·Vol. 8
·期 3
·426-432
·
IF 0.781
Hu Jinghui,Wang Li,Shen Heping,Huang Yujie,Zhao Wei
The elevated expression of mammalian target of rapamycin (mTOR) is associated with the occurrence, progression, and drug resistance of various tumors. Studies have shown overexpression of mTOR and reduced expression of miR-101 in cervical cancer tissues. Bioinformatic analysis has revealed
that a targeting binding site exists between miR-101 and the 3'-UTR of mTOR mRNA. In this study we determined whether miR-101 played a role in regulating mTOR expression and influencing the proliferation, apoptosis, and drug resistance to cisplatin (DDP) of CC cells. The regulatory relationship
between miR-101 and mTOR was validated by dual-luciferase reporter gene assay. The DDP resistance cell line, CaSki/DDP, was established, and the expressions of miR-101, mTOR, p-mTOR, and p-4EBP1 in the CaSki/DDP cell line and parental CaSki cells. The effect of DDP treatment on the proliferation
and apoptosis of the two cell lines were detected by flow cytometry. CaSki/DDP cells were divided into the following four transfection groups: miR-NC group; miR-101 mimic group; si-NC group; and si-mTOR group. The expression of miR-101, MTOR, p-mTOR, and p-4EBP1 was determined, and the effect
of DDP treatment on the proliferation and apoptosis of the two cell lines we detected by flow cytometry. There was a targeted regulatory relationship between miR-101 and mTOR. The expression and apoptosis rate of miR-101 in CaSki/DDP cells were significantly lower than CaSki cells, while the
expression and proliferation of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells were significantly higher than CaSki cells. The transfection of miR-101 mimic or si-mTOR significantly reduced the expression of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells and weakened the cell proliferation ability.
DDP treatment significantly increased the apoptosis rate. The decreased expression of miR-101 is associated with CaSki/DD cell resistance to DDP. Overexpression of miR-101 can reduce the resistance of cervical cancer CaSki/DDP cells to DDP by targeted inhibition of the expression of mTOR.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 7
·e70539
·
IF 4.2
Yingjie Shen,Yitong Zhou,Kuziwakwashe Alice Chiwa,Junxin Wang,Shihong Ren,Mingxuan Wang,Hongru Ren,Yeyi Zheng,Ying Yu,Lutao Jiang,Jingmou Yu,Yuchun Qiao,Litai Jin,Jianlin Lou,Xiangkuo Zheng
Psoriasis is an immune-mediated inflammatory dermatological disorder characterized by the interaction between immune cells and keratinocytes, which perpetuates cutaneous inflammation and cellular hyperproliferation. In this study, we identified a strong δ-catenin signature in psoriatic skin; however, the precise role of δ-catenin remains to be elucidated. Additionally, we observed that Interleukin (IL)-17A, a pivotal cytokine involved in the development of psoriatic lesions, induces δ-catenin expression in HEKn and HACAT cells. From a mechanistic perspective, δ-catenin initiated NF-κB signaling, subsequently leading to the activation of IL-6 and IL-8 production. Furthermore, silencing δ-catenin expression mitigated IL-17A-induced hyperproliferation of keratinocytes through the NF-κB pathway. Our study further identified miR-101 and miR-122 as upstream regulators of δ-catenin, exerting their effects by downregulating δ-catenin protein levels. We demonstrated that miR-101 and miR-122 can inhibit the hyperproliferation of keratinocytes induced by δ-catenin. These findings validate the role of δ-catenin in the pathogenesis of psoriasis, particularly in keratinocyte-mediated inflammatory responses and cellular hyperproliferation. Consequently, miR-101 and miR-122 hold potential as therapeutic agents in the treatment of psoriasis. Graphical The schematic diagram delineates the signaling pathway associated with IL-17A-induced psoriasis, highlighting the upregulation of delta-catenin, which initiates NF-κB signaling. This activation subsequently leads to the production of IL-6 and IL-8, as well as the hyperproliferation of keratinocytes. Furthermore, miR-101 and miR-122 function as inhibitors of delta-catenin, effectively obstructing this signaling cascade.
研究领域:
皮肤病学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 23
·11079-11090
·
IF 7.233
Jingpu Zhang,Yanlei Liu,Xiao Zhi,Chunlei Zhang,Tie Fu Liu,Daxiang Cui
Dysregulation of microRNAs (miRNAs) is correlated with cancer progression. In vitro detection methods using extracts from cell lysis cannot provide information about the spatial distribution of miRNAs. Due to the development of miRNA fluorescence in situ hybridization (FISH), increasing amounts of intracellular expression information are being obtained. However, miRNA FISH suffers from weak signals and complex steps and thus remains very challenging. Herein, a strategy based on DNA-templated silver nanoclusters (AgNCs/DNAs) and their G-rich fluorescence enhancement effect was developed for FISH detection of miRNAs in gastric cancer cells. The method combines hybridization and signal amplification into one step, which allows imaging of intracellular miRNAs immediately after hybridization. Most importantly, using the method based on our design, miR-101-3p, miR-16-5p and miR-19b-3p were found to be located in the nuclei of MGC803 cells with granulated shapes, indicating an unanticipated distribution pattern. In addition, before the final miRNA FISH, we performed an optimization of AgNCs/DNAs and their G-rich fluorescence enhancement effect; we found that the effect occurred at shorter wavelengths emitting green fluorescence, with weakened red fluorescence at longer wavelengths. However, the components involved in the FISH process impacted the fluorescence properties so greatly that the probes finally exhibited slightly strengthened red fluorescence signals. Our method enables facile visualization of miRNAs at the subcellular level, which may benefit the precise localization of miRNAs in single cells in the future.
研究领域:
癌症生物学
·
分子生物学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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