EUROPEAN JOURNAL OF PHARMACOLOGY
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2021
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IF 4.432
Liwei Ni,Jianhao Xu,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jie Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
MicroRNAs (miRNAs) are involved in the initiation and development of cancer and participate in drug resistance. Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The abnormal miRNA expression in NSCLC and its association with chemotherapy drug resistance remains largely unknown. The study aimed to investigate the aberrant expression of miR-221–3p in NSCLC and to elucidate its molecular mechanisms in relation to PTX resistance. PTX increased miR-221–3p expression and regulated MDM2/P53 expression in the PTX-sensitive NSCLC strain (A549). Meanwhile, miR-221–3p was rarely expressed and not interfered by PTX in PTX-resistant A549 cells (A549/Taxol). Dual-luciferase reporter assay confirmed that miR-221–3p specifically binds to MDM2 messenger RNA and inhibited MDM2 expression. The expression of MDM2 and P53 showed a negative correlation in NSCLC cell lines. MiR-221–3p down-regulation reduced the sensitivity of A549 cells to PTX, whereas its up-regulation partially reversed the A549/Taxol cells resistance to PTX and increased the chemosensitivity of A549/Taxol cells to PTX in xenograft models. Quantitative polymerase chain reaction analysis revealed that miR-221–3p expression increased, whereas the MDM2 level decreased in human NSCLC tumor tissues. Moreover, Western bolt analysis showed that P53 was lowly expressed in tumor tissues with MDM2 overexpression. Low expression of miR-221–3p in NSCLC tissues might indicate a poor T staging. In conclusion, miR-221–3p overexpression could regulate MDM2/p53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·1-22
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IF 15.7
Wang Wenkai,Cheng Zhuo,Yu Miao,Liu Ke,Duan Hongli,Zhang Yang,Huang Xinle,Li Menghuan,Li Changqing,Hu Yan,Luo Zhong,Liu Minghan
Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral disc degeneration (IDD). We discover that nucleus pulposus progenitor cells (NPPCs) could imprint ferroptosis resistance into NPCs through exosome-dependent intercellular transmission of miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression and NPC uptake capacity, which are integrated into an injectable hydrogel based on extracellular matrix (ECM) analogues. The ECM-mimetic hydrogel (HACS) serves as a biomimetic filler for the post-operative care of herniated discs, which could be facilely injected into the discectomy-established nucleus pulposus (NP) cavity for localized treatment. HACS-mediated in-situ exosome release in the NP cavity enables marked ferroptosis inhibition in NPCs that not only prevents LDH recurrence but also reverses the IDD symptoms, leading to robust restoration of NP structure and functions. In summary, this study offers a promising approach for treating disc herniation.
研究领域:
医学
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生物材料学
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DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2026
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IF 6.2
Lingyun Zhao,Anqi Li,Shijing Chen,Wei Hua,Ru Dai,Lingyu Pan,Meng Hu,Nan Huang,Runke Zhou,Yuanyuan Han,Lidan Xiong,Li Li
Stem cells and their paracrine factors hold promise for alopecia treatment, yet research on human skin-derived precursors (hSKPs), which are closely related to hair follicles in biological positioning and function, remains limited. We demonstrated that extracellular vesicles of human transformed skin-derived precursors (htSKP-EVs), harvested utilizing our directed induction, culture transition and gradient ultracentrifugation technology, exhibited superior efficiency and quality determined by transmission electron microscopy, nanoparticle tracking analysis, and detection of specific markers. Using CCK8, scratch assay, immunofluorescence, H&E staining, immunohistochemistry staining, dermoscope, qRT-PCR and Western blotting, it was found that htSKP-EVs significantly promoted the proliferation of hair follicle stem cells (hHFSCs) by effectively modulating the Wnt signaling pathway, thereby enhancing overall hair follicle growth. Notably, miR-221-3p, highly expressed in htSKP-EVs, suppressed DKK2 expression, activated the Wnt pathway in human dermal papilla cells (hDPCs), and induced hair follicles to enter and sustain the anagen phase, based on the aforementioned similar in vivo and in vitro experiments. These findings, validated in hHFSCs, hDPCs and human hair follicles in vitro and in a murine alopecia model in vivo, revealed the potential mechanism of htSKP-EVs in hair growth and identified a new therapeutic target for alopecia in regenerative medicine.
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DOI
高影响因子
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