CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
·
2020
·Vol. 35
·期 9
·650-660
·
IF 2.314
Suiyang Zhou,Aili Xu,Tiefang Song,Fei Gao,Haizhu Sun,Xianchao Kong
Background: MIAT (myocardial infarction-associated transcript) regulates cell proliferation, apoptosis, and metastasis in several cancers. In this study, the authors aimed to explore the role of MIAT in ovarian cancer.Materials and Methods: The expression of MIAT in ovarian cancer subtypes, normal human ovarian surface epithelial and ovarian cancer cell lines was measured by qualitative real-time polymerase chain reaction (qRT-PCR). OVCAR3 and SKOV3 cells were transfected with MIAT overexpression plasmid or siMIAT. The cell growth ability was then evaluated by CCK-8 and colony formation assays. The cell migration and invasion rate were separately measured by wound-healing and transwell assays. The levels of epithelial–mesenchymal transition (EMT)-associated markers were evaluated by Western blotting. MIAT sponging miR-150-5p was predicted by starBase and confirmed by dual-luciferase reporter assays. The expression of miR-150-5p in OVCAR3 and SKOV3 cells with MIAT overexpression or knockdown, and in ovarian cancer subtypes was also measured by qRT-PCR. Further analyses confirmed the role of MIAT sponging miR-150-5p in ovarian cancer cells.Results: MIAT was highly expressed in mesenchymal subtype ovarian cancer tissues and ovarian cancer cells. In OVCAR3 and SKOV3 cells, overexpression of MIAT promoted, and knockdown of MIAT suppressed the cell growth, migration, invasion, and EMT. miR-150-5p was sponged and regulated by MIAT. miR-150-5p was downregulated in mesenchymal subtype ovarian cancer. Suppression of cell migration, invasion, and EMT caused by miR-150-5p overexpression was rescued by MIAT overexpression.Conclusions: MIAT acts as an oncogene in ovarian cancer cells through sponging miR-150-5p. MIAT or miR-150-5p expression might be a potential prognostic biomarker for ovarian cancer patients. MIAT and miR-150-5p are potential therapeutic targets in treatment of ovarian cancer.
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BMC CANCER
·
2021
·Vol. 21
·期 1
·1-14
·
IF 4.43
Zhao Wei,Zhao Jing,Guo Xiao,Feng Yujie,Zhang Bingyuan,Tian Lantian
Background Cholangiocarcinoma is a common malignant tumor of digestive system. LncRNA metallothionein 1 J, pseudogene (MT1JP) has been reported to play tumor-suppressing roles in multiple cancers. However, its effect on cholangiocarcinoma has not been evaluated. Methods The expression of MT1JP in intrahepatic cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into intrahepatic cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xenograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude mice. Results MT1JP was downregulated in intrahepatic cholangiocarcinoma specimens, and its expression was related with TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in intrahepatic cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in intrahepatic cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice. Conclusions MT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axis. These findings may provide novel insights for clinical diagnosis and treatment of cholangiocarcinoma.
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Frontiers in Cell and Developmental Biology
·
2020
·
IF 5.186
Zhai Qiaoli,Zhao Yi,Wang Linping,Dai Yan,Zhao Peiqing,Xiang Xinxin,Liu Kui,Du Wenyan,Tian Wenxiu,Yang Baoye,Li Tao,Wang Lianqing
Circular RNAs (circRNAs) are regarded as pivotal regulators in bone metabolism. However, the role of circRNAs in osteoblast mineralization remains largely unknown. Herein, we explored the expression profiles of circRNAs in 4 groups of osteoblasts with varying mineralization processes. Hsa_circ_0008500 (circ8500), which is upregulated in the RNA-seq data, is sifted through 194 candidate circRNAs in osteoblasts during mineralization. We characterize the features of novel circRNAs and find that the elevated expression of circ8500 promotes osteoblast mineralization. Mechanistically, circ8500 contains a critical binding site for miR-1301-3p. We further show that circ8500 competitively binds miR-1301-3p to abolish its suppressive effect on peptidyl arginine deiminase 4 (PADI4). PADI4 works as a binding partner of RUNX2 and stabilizes its protein expression levels by inhibiting the ubiquitin-proteasome pathway. This work provides new insights on the circRNA patterns in osteoblasts and the role of PADI4 in matrix mineralization.
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FOLIA NEUROPATHOLOGICA
·
2020
·Vol. 58
·期 1
·70-82
·
IF 1.278
Yanxiang Zhang,Qi Chen,Yu Nai,Chunni Cao
IntroductionThe polarization state of microglia affects the progress of neuropathic pain. MiR-155 modulates polarization of microglia, while its role in neuropathic pain has not been well studied.Material and methodsWe separately used lipopolysaccharide (LPS) and interleukin 4 (IL-4) for constructing an M1/M2 polarization model in BV-2 cells. The levels of CD86, iNOS, CD206, Arg and miR-155 were measured by western blot or qRT-PCR, as needed. Subsequently, BV-2 cells were transfected with miR-155 mimics or inhibitor to explore the effects of miR-155 on polarization states. We also constructed a neuropathic pain model by applying spinal nerve ligation (SNL) in Wistar rats with miR-155 agomir or antagomir injection. The withdrawal threshold was measured by Von Frey fibre needle. The levels of interleukin 1b (IL-1b), tumour necrosis factor a (TNF-a) and the proportion of M1-polarized microglia in primary microglia from rats were measured by ELISA and flow cytometry.ResultsLPS induced M1 polarization in BV-2 cells with increasing of CD86, iNOS and miR-155, while IL-4 induced M2 polarization in BV-2 cells with increasing of CD206, Arg and decreasing of miR-155. MiR-155 mimics upregulated CD86 and downregulated CD206, whereas miR-155 inhibitor downregulated CD86 and upregulated CD206. MiR-155 antagomir increased the withdrawal threshold, decreased the production of IL-1b, TNF-a and the proportion of M1-polarized microglia in primary microglia.ConclusionsResults demonstrate that suppression of miR-155 attenuates neuropathic pain by inducing an M1 to M2 switch in microglia. Our findings provide a new perspective to understand the function of miR-155 in microglia.
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Bioengineered
·
2020
·
IF 2.205
Bing Han,Yang Ge,Junpeng Cui,Baolin Liu
Long non-coding RNAs (lncRNAs) play a key role in the development and metastasis of cancer. However, the biological role and clinical significance of lncRNA DNAJC3-AS1 in the development of colon cancer is still unknown. In this study, the effects of DNAJC3-AS1 on cell proliferation, migration, and invasion were evaluated by MTT assay, wound-healing assay, and transwell assay, respectively. The relationship between DNAJC3-AS1, miR-214-3p and LIVIN was predicted by the online software and confirmed by dual-luciferase reporter assay. We found that the down-regulation of DNAJC3-AS1 inhibited the proliferation of colon cancer cells and induced growth arrest. Down-regulation of DNAJC3-AS1 also inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells. Moreover, miR-214-3p can bind to DNAJC3-AS1, and knockdown of DNAJC3-AS1 increased miR-214-3p expression in colon cancer cells. LIVIN was identified as a target of miR-214-3p. The up-regulation of miR-214-3p inhibited the protein expression of LIVIN and suppressed the activation of the NF-κB signaling pathway. Besides, down-regulation of DNAJC3-AS1 reduced cell viability, invasion, and EMT of colon cancer cells, while miR-214-3p inhibitor could reverse these effects. The expression of LIVIN and the activation of the NF-κB signaling pathway were suppressed by down-regulating DNAJC3-AS1, while these effects could be restored by miR-214-3p inhibitor. These findings suggested that DNAJC3-AS1 may promote colon cancer progression by regulating the miR-214-3p/LIVIN axis. DNAJC3-AS1 may serve as a new biomarker and therapeutic target for colon cancer, stimulating new research directions and treatment options.
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International Journal of Nanomedicine
·
2024
·
IF 6.6
Guoqiang Xu,Xiaona Song,Xiaotang Wang,Rui Xue,Xiaoru Yan,Litao Qin,Xiaoqi Chang,Jiping Gao,Zhaoyang Chen,Guohua Song
Purpose Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.
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Biomaterials Science
·
2017
·Vol. 5
·期 11
·2268-2275
·
IF 4.21
Haobo Han,Jiebing Yang,Yudi Wang,Wenqi Chen,Jiawen Chen,Yan Yang,Quanshun Li
The nucleobase analogue 2-amino-6-chloropurine was modified on the surface of polyamidoamine (PAMAM) to construct a derivative AP-PAMAM, and then it was used as a gene carrier for miR-23b delivery to achieve the anti-tumor effects. The carrier AP-PAMAM could condense miR-23b into stable nanoparticles with a particle size of 97.3 nm (N/P ratio of 50), which was favorable for the cellular uptake of nanoparticles. Compared with PAMAM, AP-PAMAM exhibited an obviously enhanced transfection efficiency through the transfection assay of plasmids pEGFP-N3 and pGL-3. Using the human lung adenocarcinoma cell line A549 as a model, AP-PAMAM-mediated miR-23b delivery could achieve a stronger anti-proliferative effect than PAMAM/miR-23b. The inhibition of cell proliferation was elucidated to be associated with the apoptotic induction (apoptotic ratio of 23.2%) and S phase arrest owing to the decreased expression level of cyclin D1. Meanwhile, the AP-PAMAM-mediated miR-23b delivery could suppress the cell migration and invasion of cancer cells through wound healing and Transwell migration assays. In summary, the PAMAM derivative-mediated miR-23b delivery could be a promising strategy for achieving tumor gene therapy.
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Frontiers in Bioscience-Landmark
·
2024
·Vol. 29
·期 8
·278
·
IF 3.3
Feng Long,Hailong Li,Xujun Chen,Yiqun He,Youhai Dong
Background: Bone tissue engineering offers a new approach for the treatment of bone defects, with angiogenesis being critical to the survival and development of tissue-engineered bone. Mineralized osteoblasts (MOBs) have been reported to promote vascular formation by endothelial cells (ECs) through the secretion of exosomes containing a variety of angiogenic factors. The aim of the present study was to investigate the effect of miR-423-5p contained within exosomes derived from MOBs (MOB-Exos) on EC angiogenesis. Methods: The Cell Counting Kit-8 (CCK-8), scratch wound healing, Transwell migration, and tube formation assays were conducted to assess the in vitro effects of MOB-Exos on EC proliferation, migration, and tubule-forming capabilities. The miR-423-5p level in MOB-Exos was quantified using quantitative polymerase chain reaction (qPCR). Co-culture experiments were used to study the exosomal transport of miR-423-5p and its angiogenic effects. High-throughput sequencing was used to identify differentially expressed genes, and a dual luciferase reporter assay to determine whether CXCL10 was a direct target gene for miR-423-5p. Furthermore, the in vivo effect of MOB-Exos-derived miR-423-5p on angiogenesis was evaluated using a subcutaneous xenograft model. Results: MOB-Exos significantly promoted the in vitro proliferation, migration, and tubule formation of ECs. A high level of miR-423-5p was found in MOB-Exos and promoted the angiogenesis of ECs. The CXCL10 gene was significantly downregulated in ECs upon miR-423-5p mimic transfection. Dual luciferase reporter assay confirmed the direct binding of miR-423-5p to the CXCL10 gene. miR-423-5p derived from MOB-Exos upregulated expression of the vascular markers CD31 and vascular endothelial growth factor (VEGF) in vivo, thus underscoring its angiogenic potential. Conclusion: This study found that miR-423-5p derived from MOB-Exos could potentially enhance EC angiogenesis via the regulation of CXCL10. Therefore, exosomes are promising therapeutic candidates for clinical bone defects.
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Experimental and Therapeutic Medicine
·
2024
·Vol. 28
·期 3
·1-11
·
IF 2.4
Wenxian Tu,Meina Feng,Qin Zhou,Yunfeng Wang,Mingye Wan,Danqun Gong,Jin Li,Yuanmin Du
Evidence has shown that microRNAs (miRNAs/
miRs) play key roles in biological functions of vascular smooth muscle cells (VSMCs). However, the role of miR‑374a in VSMCs remains to be elucidated. The present study aimed to explore the influence of miR‑374a on VSMCs and its molecular mechanism. The expression level of miR‑374a was measured by reverse transcription‑quantitative (RT‑q) PCR. MTT and Transwell assay were employed to assess the role of miR‑374a in proliferation and migration of VSMCs. To order to determine miR‑374a targets, a dual‑luciferase reporter assay was conducted, which was further verified by rescue experiments. Chromatin Immunoprecipitation Assay and JASPAR databases were applied to explore the regulatory association between GATA binding protein 2 (GATA2) and miR‑374a. Western blotting or RT‑qPCR were employed to detect the protein expression levels of GATA2 or RAR‑related orphan receptor A (RORA). The present study found that miR‑374a was elevated in VSMCs following treatment with platelet‑derived growth factor‑BB (PDGF‑BB) compared with that in control group. In addition, the results demonstrated that a higher expression of a miR‑374a could promote proliferation and migration of VSMCs while miR‑374a inhibitor suppressed the PDGF‑BB‑induced proliferation and migration of VSMCs in vitro. Furthermore, circTADA2A bound to miR‑374a and then upregulated RORA expression, which resulted in inhibition in VSMCs proliferation and migration. On the other hand, the result indicated that GATA2 overexpression could augment the proliferation, migration of PDGF‑bb‑induced VSMCs, which could be rescued by miR‑374a inhibitor. The findings suggested that the GATA2/circTADA2A‑miR‑374a axis promoted the proliferation and migration of VSMCs by targeting RORA, which were closely related to atherosclerosis (AS). Thus the results might offer a new therapeutic target for AS.
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MEDIATORS OF INFLAMMATION
·
2025
·Vol. 2025
·期 1
·4955849
·
IF 4.2
Zhengrong Chen,Dingwei Yan,Suyu Guo,Yiyi Song,Xinxing Zhang,Wenjing Gu,Heting Dong,Li Huang
Background: This study aimed to explore the mechanisms underlying T-cell differentiation in asthma. Methods and Results: Flow cytometry was performed to detect Th cells. LC-MS/MS was performed to assess lipid metabolism. HE staining was performed to assess the pathological changes of the lung tissues. ELISA was performed to detect cytokine levels. The results of quantitative real-time polymerase chain reaction (qRT-PCR) and western blot showed that miR-192-5p expression was decreased, while SCD1 expression was increased in CD4 + T cells isolated from the peripheral blood of children with asthma. The dual luciferase reporter assay determined the direct interaction between miR-192-5p and SCD1. MiR-192-5p inhibitor reduced ASCL3 and PPARα, increased FASN and SREBP1c mRNA expression and protein levels in mouse spleen CD4 + T cells, and elevated Th2 and Th17 cells, but these effects were reversed by the SCD1 inhibitor. Oleic acid (OA) reduced Th1 cells and increased Th2 and Th17 cells in mouse spleen CD4 + T cells treated with an SCD1 inhibitor. Additionally, pri-miR-192-5p expression was increased in CD4 + T cells isolated from the peripheral blood of asthmatic children, and the deletion of METTL3 upregulated pri-miR-192-5p expression in an m6A-dependent manner. MiR-192-5p mimic and inhibitor both reversed miR-192-5p and SCD1 expression affected by overexpression or deletion of METTL3, both in vivo and in vitro . Furthermore, METTL3 overexpression attenuated lung inflammation, elevated Th1 cells, and reduced Th2 and Th17 cells in CD4 + T cells isolated from the peripheral blood of asthmatic mice. These effects were reversed by the miR-192-5p inhibitor. Conclusion: These results suggest that METTL3/miR-192-5p/SCD1 axis regulates lipid metabolism and affects T cell differentiation, thus affecting asthma progression. This study may provide novel insights into the pathogenesis of asthma and a new treatment strategy.
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International Journal of Nanomedicine
·
2025
·
IF 6.5
Dong Zheng,Tong Chen,Kaiyuan Yang,Guangrong Yin,Yang Chen,Jianchao Gui,Chao Xu,Songwei Lv
Introduction: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration. Chondrocyte inflammation, apoptosis, and extracellular matrix degradation accelerated OA progression. MicroRNA (miRNA) has the potential to be a therapeutic method for osteoarthritis. However, it is difficult to penetrate the cell to exercise its biological function, and its extracellular effect is unclear.Methods: lipo-AgPEI-miR-200c-3p was created by combining miR-200c-3p with silver nitrate polyvinylimine nanoparticles on a microfluidic device. The drug release curve, stability, temperature sensitivity, cytotoxicity, and the impact of lipo-AgPEI-miR-200c-3p on the expression of proteins linked to matrix disintegration, apoptosis, and inflammatory factors were all detected.Results: Results showed that the particle size of Lipo-AgPEI-miR-200c-3p was about 130 nm, the Zeta potential was lowered to 1.08± 0.12 mV. Lipo-AgPEI-miR-200c-3p could increase cell viability, prevent cell apoptosis, and decrease the expression levels of TNF-α, IL-6, IL-1β, and MCP-1 in ADTC5 cells following LPS stimulation. MMP3, MMP13, and ADAMTS-4 expression was downregulated whereas collagen II expression was upregulated. The ZEB2 expression was greatly elevated following LPS stimulation and dramatically decreased following transfection of miR-200c-3p. Collagen II expression rose following transfection of si-ZEB2, whereas the expression levels of inflammatory factors, apoptosis-related proteins, MMP3, MMP13, and ADAMTS-4 decreased. The dual luciferase experiment demonstrated that ZEB2 was the target gene of miR-200c-3p.Conclusion: The synergistic effect of AgPEI and miR-200c-3p can inhibit the inflammatory response, apoptosis, and matrix degradation of chondrocytes. Lipo-AgPEI-miR-200c-3p can also improve transfection efficiency and obtain good physicochemical properties of drugs. miR-200c-3p may be crucial in the development of OA and can influence the target gene ZEB2, control the inflammatory response, apoptosis, and chondrocyte matrix breakdown.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Li Chao,Xiang Zhenyang,Hou Mengfan,Yu Hao,Peng Peng,Lv Yigang,Ma Chao,Ding Han,Jiang Yunpeng,Liu Yang,Zhou Hengxing,Feng Shiqing
Background Spinal cord injury (SCI) often leads to a loss of motor and sensory function. Axon regeneration and outgrowth are key events for functional recovery after spinal cord injury. Endogenous growth of axons is associated with a variety of factors. Inspired by the relationship between developing nerves and blood vessels, we believe spinal cord-derived microvascular endothelial cells (SCMECs) play an important role in axon growth. Results We found SCMECs could promote axon growth when co-cultured with neurons in direct and indirect co-culture systems via downregulating the miR-323-5p expression of neurons. In rats with spinal cord injury, neuron-targeting nanoparticles were employed to regulate miR-323-5p expression in residual neurons and promote function recovery. Conclusions Our study suggests that SCMEC can promote axon outgrowth by downregulating miR-323-5p expression within neurons, and miR-323-5p could be selected as a potential target for spinal cord injury repair. Graphical Abstract
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