Biomaterials Science
·
2022
·Vol. 10
·期 13
·3637-3646
·
IF 7.59
Qingyan Zhang,Ying Huang,Ruoxi Yang,Junmei Mu,Zhanwei Zhou,Minjie Sun
Despite the great progress in the control of primary tumor growth, metastasis remains the major challenge of breast cancer therapy in clinics, which is highly related to the upregulation of reactive oxygen species (ROS) and overexpression of its relevant pro-survival miR-155 gene. Therefore, we fabricated a poly-antioxidant (FTP) to deliver anti-miR-155 for synergistic treatment of metastatic breast cancer by ROS scavenging and miR-155 inhibition. FTP was synthesized by the polymerization of fluorated-polyethyleneimine (FPEI) and antioxidants (TEMPOL), using a glutathione (GSH) responsive linker for controlled drug release. Notably, the poly-drug strategy could not only promote the tumoral accumulation of small molecular antioxidants but also enhance the transfection efficiency of anti-miR-155 owing to the hydrophobic property of TEMPOL. After synergistic treatment, the NF-κB pathway was significantly blocked, thereby generating strong anti-metastatic ability both in vitro and in vivo. The poly-antioxidant could be a new type of nanoplatform for highly efficient and safe miRNA delivery, which also provides a promising strategy for the synergistic treatment of metastatic breast cancer.
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Yang Jianru,Jia Yang,Wang Bing,Yang Shengrong,Du Kun,Luo Yujie,Li Yunhe,Zhu Bing
Background: The effects of up-regulated CircCHST15 on lung cancer remained unclear. In this study, the role of CircCHST15 in lung cancer was investigated.Methods: Dual-luciferase reporter verified the bioinformatics prediction that CircCHST15 targeted miR-155-5p and miR-194-5p. The correlation between CircCHST15 and PD-L1 was analyzed by Pearson analysis. CCK-8 and colony formation was performed to determine the viability and proliferation of lung cancer cells. After the lung cancer (subcutaneous-xenotransplant) model was established in mice, the T cell subtype and related cytokines in mouse tumor tissues were detected by flow cytometry and ELISA. Moreover, the expressions of CircCHST15, miR-155-5p, miR-194-5p, immune-related, and proliferation-related factors of the lung cancer cells or mice tumor tissues were detected by immunohistochemistry, RT-qPCR, or Western blot.Results: CircCHST15 and PD-L1 were high-expressed in lung cancer, and the two was positively correlated. CircCHST15 targeted miR-155-5p and miR-194-5p, the later further targeted PD-L1. Lung cancer cell viability and proliferation were increased by miR-155-5p and inhibited by miR-194-5p. CircCHST15 located in the cytoplasm promoted tumor growth, down-regulated the expressions of miR-155-5p and miR-194-5p, and up-regulated the expressions of PD-L1, Ki-67, PCNA, CCL17, CCL22, IFN-γ, TNF-β, and IL-10. Also, CircCHST15 decreased the CD8+ cells in mouse blood and tumor, but increased the Tregs in mouse tumor. PD-L1 inhibitor showed an opposite effect to CircCHST15 on mouse tumors.Conclusion: CircCHST15 sponged miR-155-5p and miR-194-5p to promote the PD-L1-mediated immune escape of lung cancer cells.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Hua-yang Fan,Ming-da Zhao,Hong-jie Jiang,Zhen-wei Yu,Yu-jiang Fan,Xin-hua Liang,Ya-ling Tang,Yong Sun
Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.
研究领域:
肿瘤学
·
分子生物学
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2021
·
IF 2.329
Yaxin Guo,Dan Liu,Qing Yang,Wei Shi,Zhihui Yang,Jia Chen,Juan Xiang
Serum miR-501-3p and miR-455-3p are potential biomarkers for the diagnosis of Alzheimer’s disease (AD). The combination of both microRNAs (miRNAs) is anticipated to improve AD diagnostic accuracy and provide stage information. In this work, simultaneous determination of both miRNAs was performed using a dual-signal DNA probe based on the fluorescent recovery of carbon quantum dots (CQDs) and the sulfo-cyanine5 (Cy5) dye. Duplex specific nuclease was introduced to amplify the signals via a DNA degradation/RNA re-hybridization cycle. The dynamic ranges of the method were 0.01 to 4 pM for miR-501-3p and 0.01 to 5 pM for miR-455-3p. The accuracy of the method was confirmed by the recoveries of the miRNAs in spiked human serum and high correlation with measurements by the real-time quantitative reverse transcription–polymerase chain reaction (qRT-PCR). The concentrations of the miRNAs were determined in serum from healthy donors and AD patients in preclinical and mild stages. Detailed t-test analysis revealed that despite of the poor correlations of independent miR-501-3p and miR-455-3p with AD progression, the concentration ratio of miR-501-3p to miR-455-3p was significantly correlated with AD diagnosis (p < 0.001 between preclinical AD and healthy control) and early progression (p < 0.001 between preclinical and mild-stage AD). A simple, sensitive method is reported for the simultaneous determination of the miRNAs in serum with high accuracy and shows that the concentration ratio of miR-501-3p to miR-455-3p is an effective blood index for early and in-stage diagnosis of AD.
研究领域:
生物化学
·
分子生物学
·
神经科学
·
诊断医学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Huanling Guo,Ming Xu,Zhong Cao,Wei Li,Lida Chen,Xiaoyan Xie,Wei Wang,Jie Liu
Ultrasound-induced microbubble sonoporation has been shown to effectively improve drug/gene delivery efficiency by enhancing tissue and cell permeability. However, the microscale size and short duration of ultrasound contrast agents limit their accumulation in target areas. Here, a kind of ultrasound-triggered phase-transitioning and size-changing cationic nanodroplet, perfluoropentane/C9F17-PAsp(DET)/miR-122/poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets (PFP-TNDs/miR-122), was developed to deliver microRNA-122 (miR-122) for hepatocellular carcinoma (HCC) treatment. PFP served as an ultrasound-sensitive core for ultrasound-triggered phase transition and size change from the nanoscale to the microscale. Positively charged C9F17-PAsp(DET) ensured adequate miRNA loading. PGA-g-mPEG, which served as the shell of the nanodroplet, modified the nanodroplets, enhanced their stability in serum, and protected miR-122 from degradation in vivo. The results exhibited that PFP-TNDs/miR-122 has a nanosize diameter (362 ± 15 nm) and remained stable for 24 h. After treatment with PFP-TNDs/miR-122 combined with ultrasound irradiation, the miR-122 expression level was significantly increased by approximately 600-fold in HepG2 cells, 500-fold in SMMC-7721 cells, and 30-fold in human HCC xenografts. Moreover, PFP-TNDs/miR-122 combined with ultrasound radiation effectively suppressed the growth, migration, and invasion of HCC cells, and inhibited tumor proliferation in mice. This study revealed that the biodegradable PFP-TNDs is a promising therapeutic gene carrier with functions of gene protection and effective gene delivery for clinical applications. Furthermore, PFP-TNDs/miR-122 associated with ultrasound irradiation may pave a new way to improve the prognosis of patients with HCC.
研究领域:
医学
·
生物技术
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Qiaohui Ren,Xinyue Zhu,Nannan Wang,Kang Yu,Wei Lv,Lianzi Wang,Yan Zang,Dongyue Ma,Xinyi Zhou,Junxiao Yao,Mengjiao Shen,Li Yu,Tao Li
Purpose We explored the effects of miR-133a-5p and ATP7B on cuproptosis in hepatocellular carcinoma.Methods Initially, we assessed the impact of miR-133a-5p on hepatocellular carcinoma (HCC) using CCK-8 assays, cell scratch assays, and flow cytometry. Subsequently, we utilized elesclomol in combination with copper ions to induce cuproptosis in the HCC cell lines PLC/PRF/5 and Huh-7. We evaluated the influence of miR-133a-5p on cuproptosis using CCK-8 assays, cell scratch assays, flow cytometry, and Western blotting. To elucidate the underlying mechanisms, we employed bioinformatics to identify potential downstream target genes of miR-133a-5p and conducted dual-luciferase reporter assays to confirm the binding sites. Finally, we validated the regulatory effect of miR-133a-5p on ATP7B by modulating miR-133a-5p expression through cell transfection experiments.Results The results from the CCK-8 assay, cell scratch assay, and flow cytometry demonstrated that miR-133a-5p significantly inhibits the proliferation and migration of HCC cells while promoting their apoptosis. Furthermore, Elesclomol in combination with copper ions induces cuproptosis in HCC cells. Compared to the cuproptosis observed in HCC as a control, miR-133a-5p further suppresses the proliferation and migration of HCC cells, enhances their death, and increases the expression of cuproptosis-related proteins more prominently. Bioinformatics analysis suggested that ATP7B might be a downstream target gene of miR-133a-5p. This was confirmed by dual luciferase assays, which identified a binding site between miR-133a-5p and ATP7B. Additionally, the expression levels of ATP7B were found to decrease or increase in response to the regulation by miR-133a-5p.Conclusion MiR-133a-5p facilitates cuproptosis in hepatocellular carcinoma through targeting of ATP7B.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Surgical Oncology
·
2021
·Vol. 19
·期 1
·1-14
·
IF 2.754
Zhang Weitong,Wang Zhenfen,Cai Guohao,Huang Ping
Background Circular RNAs (circRNAs) take part in colorectal cancer malignancies. CircRNA dedicator of cytokinesis 1 (circ_DOCK1) is involved in colorectal cancer progression, but the mechanism underlying this circRNA that takes part in colorectal cancer development remains largely undetermined.Methods Tumor and normal para-cancerous tissues were collected from 42 colorectal cancer patients. Human colorectal cancer cell lines (HCT116 and SW480) were used for the experiments in vitro. Circ_DOCK1, microRNA (miR)-132-3p, and ubiquitin-specific protease 11 (USP11) levels were measured through quantitative real-time polymerase chain reaction and Western blotting. Cell growth, metastasis, and apoptosis were investigated via colony formation, 5-ethynyl-2′-deoxyuridine (EdU) staining, MTT, flow cytometry, Western blotting, and transwell analyses. The target association was evaluated via dual-luciferase reporter analysis, RNA pull-down, and immunoprecipitation (RIP). Xenograft assay was performed using HCT116 cells. USP11 and Ki67 levels in tumor tissues were detected via immunohistochemistry.Results Circ_DOCK1 expression was enhanced in colorectal cancer tissues and cells. Silencing circ_DOCK1 repressed cell growth, migration, and invasion, and facilitated apoptosis. Circ_DOCK1 sponged miR-132-3p, and miR-132-3p silence mitigated the effect of circ_DOCK1 interference on cell growth, metastasis, and apoptosis. MiR-132-3p targeted USP11, and circ_DOCK1 could regulate USP11 level by miR-132-3p. MiR-132-3p suppressed cell growth, metastasis, and apoptosis, and USP11 attenuated these effects. Knockdown of circ_DOCK1 decreased colorectal cancer cell xenograft tumor growth.Conclusion Circ_DOCK1 interference suppressed cell growth and metastasis, and increased apoptosis of colorectal cancer via decreasing USP11 by increasing miR-132-3p.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Shuai Chen,Peng Song,Yu Wang,Zeng Wang,Jiaming Xue,Yicheng Jiang,Yan Zhou,Jie Zhao,Liming Tang
Circular RNA (circRNA) is a special category of non-coding RNA that has garnered increasing attention in the exploration of lipid metabolism. However, the functional regulation mechanisms of circRNAs in obesity diseases remain unclear. By whole transcriptome sequencing, a total of 164 circular RNAs were found to exhibit differential expression between lean and obese individuals. RT-qPCR was used to detect significant expression of circMAPK9 in obese individuals, and it was closely related to BMI. Western blot, triglyceride detection, and Oil Red O staining were employed to investigate the role of circMAPK9/hsa-miR-1322/FTO in adipogenesis. In adipocytes, the connection between hsa-miR-1322 and circMAPK9 was verified using fluorescence in situ hybridization, luciferase reporter assay, and RNA immunoprecipitation. It was found that circMAPK9 competed for binding hsa-miR-1322 in the cytoplasm, weakening the inhibitory effect on FTO and promoting adipogenesis. Our study revealed the regulatory mechanism and important role of circMAPK9 in the process of adipogenesis.
研究领域:
分子生物学
·
基因组学
·
代谢
✓ 已验证
DOI
PubMed
高影响因子
Cells
·
2024
·Vol. 13
·期 4
·313
·
IF 5.1
Ziyan Xiao,Jinlian Liang,Rufei Huang,Derong Chen,Jiaxin Mei,Jingxian Deng,Zhaoyang Wang,Lu Li,Ziyi Li,Huan Xia,Yan Yang,Yadong Huang
Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli cell aging is still unclear. In this study, senescent Sertoli cells showed a substantial upregulation ofmiR-143-3pexpression.miR-143-3pwas found to limit Sertoli cell proliferation, promote cellular senescence, and cause blood–testis barrier (BTB) dysfunction by targeting ubiquitin-conjugating enzyme E2 E3 (UBE2E3). Additionally, the TGF-β receptor inhibitor SB431542 showed potential in alleviating age-related BTB dysfunction, rescuing testicular atrophy, and reversing the reduction in germ cell numbers by negatively regulatingmiR-143-3p. These findings clarified the regulatory pathways underlying Sertoli cell senescence and suggested a promising therapeutic approach to restore BTB function, alleviate Sertoli cell senescence, and improve reproductive outcomes for individuals facing fertility challenges.Keywords:miR-143-3p;sertoli cell;senescence;blood–testis barrier;UBE2E3
研究领域:
生殖生物学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Cell Journal
·
2021
·
IF 2.479
Sadaf Mahboudi,Kazem Parivar,Zohreh Mazaheri,Shiva Irani
Objective Numerous evidence indicates that microRNAs (miRNAs) are critical regulators in the spermatogenesisprocess. The aim of this study was to investigate Mir-106b cluster regulates primordial germ cells (PGCs) differentiationfrom human mesenchymal stem cells (MSCs). Materials and Methods In this experimental study, samples containing male adipose (n: 9 samples- age: 25-40 years)were obtained from cosmetic surgeries performed for the liposuction in Imam Khomeini Hospital. The differentiationof MSCs into PGCs was accomplished by transfection of a lentivector expressing miR-106b . The transfection of miR-106b was also confirmed by the detection of a clear green fluorescent protein (GFP) signal in MSCs. MSCs weretreated with bone morphogenic factor 4 (BMP4) protein, as a putative inducer of PGCs differentiation, to induce thedifferentiation of MSCs into PGCs (positive control). After 4 days of transfection, the expression of miR-106b , STELLA,and FRAGILIS genes was evaluated by real-time polymerase chain reaction (PCR). Also, the levels of thymocytedifferentiation antigen 1 (Thy1) protein was assessed by the western blot analysis. The cell surface expression of CD90was also determined by immunocytochemistry method. The cytotoxicity of miR-106b was examined in MSCs after 24,48, and 72 hours using the MTT assay. Results MSCs treated with BMP4 or transfected by miR-106b were successfully differentiated into PGCs. The resultsof this study also showed that the expression of miR-106b was significantly increased after 48 hours from transfection.Also, we showed STELLA, FARGILIS , as well as the protein expression of Thy1, was significantly higher in MSCstransfected by lentivector expressing miR-106b in comparison with MSCs treated with BMP4 (P≤0.05). MTT assayshowed miR-106b was no toxic during 72 hours in 1 µg/ml dose, that this amount could elevated germ cells markersignificantly higher than other experimental groups (P≤0.05). Conclusion According to this findings, it appears that miR-106b plays an essential role in the differentiation of MSCsinto PGCs.
研究领域:
分子生物学
·
生殖医学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Xiaoyin Rong,Ruixiao Li,Tianye Gong,Haonan Li,Xiaolei Zhao,Guoqing Cao,Meng Li,Bugao Li,Yang Yang,Xiaohong Guo
Circular RNA is a special category of non-coding RNA that has emerged as epigenetic regulator of adipose tissue development. However, the mechanism governing intramuscular adipogenesis of circRNA remains largely uncharted. In this study, circMEF2C(2, 3), looped by MEF2C exons 2 and 3, was identified from the pig MEF2C gene. Expression of circMEF2C(2, 3) is upregulated in early stage of intramuscular adipogenesis and muscular tissue of lean pigs (DLY pig). Subsequently, overexpression or knockdown of circMEF2C(2, 3) reflected that it participates in promoting proliferation and inhibiting adipogenic differentiation in porcine intramuscular preadipocytes and murine C3H10T1/2 cells. Mechanically, circMEF2C(2, 3) competitively combined with miR-383 and miR-671-3p to the 3′-UTR of MEF2C , which maintains MEF2C expression in regulating proliferation and adipogenesis. In summary, circMEF2C(2, 3) is a key regulator in the proliferation and adipogenic differentiation of intramuscular adipogenesis, suggesting its potential as a multi-target strategy for adipose development and associated diseases.
研究领域:
分子生物学
·
发育生物学
·
动物遗传育种
·
脂肪代谢
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）