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
MedComm-Oncology
·
2026
·Vol. 5
·期 3
·e70098
·
IF 8.5
Qiang Shen,Qu Leng,Kaihui Wu,Guorui Li,Yiyou Mao,Jun Wu,Ziyi Song,Zhihai Deng,Hangyang Peng,Jun Zou,Jiamin Wang,Ping Liu,Zihao Zou,Zhaojun Pan,Jianfeng Zhong,Yubin Li,Nan Deng,Xiangming Mao,Daojun Lv
Cuproptosis, a copper-dependent form of regulated cell death, represents a potential metabolic vulnerability in cancer. However, the upstream regulators of this process in prostate cancer (PCa) remain unclear. This study identified long noncoding RNA (lncRNA) LIPE-AS1 as a key suppressor of cuproptosis in PCa. Elevated levels of LIPE-AS1 were observed in PCa, which inversely correlated with the core cuproptosis gene ferredoxin 1 ( FDX1 ). Silencing LIPE-AS1 sensitized cells to the cuproptosis inducer elesclomol-Cu (Ele-Cu), an effect that was reversible through copper chelation. Mechanistically, cytoplasmic LIPE-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-330-3p, thereby derepressing its target MGAT5 . MGAT5 subsequently modulated the expression of cuproptosis-associated proteins FDX1, dihydrolipoamide S -acetyltransferase (DLAT), and dihydrolipoamide S -succinyltransferase (DLST). Rescue experiments demonstrated that MGAT5 overexpression (MGAT5-OE) reversed the cuproptosis sensitivity induced by LIPE-AS1 knockdown. In vivo studies revealed that LIPE-AS1 depletion synergized with elesclomol to suppress tumor growth. Collectively, the LIPE-AS1/miR-330-3p/MGAT5 axis is defined as a critical pathway restraining cuproptosis in PCa, providing a mechanistic basis for targeting this circuit to overcome therapy resistance. Graphical LIPE-AS1 is markedly upregulated and serves as a competitive endogenous RNA that sponges miR-330-3p. This sequestration relieves miR-330-3p-mediated repression of MGAT5, leading to elevated MGAT5, which subsequently suppresses cuproptosis-related proteins FDX1, DLAT, and DLST, thus diminishing cuproptosis sensitivity. Importantly, disrupting this axis with Elesclomol enhances cuproptosis and suggests a potential therapeutic strategy for this malignancy.
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Kaiwen Yang,Yifan Zhao,Chuyao Wang,Yeke Yu,Xiaoyu Zhang,Jie Liu,Chuan Lu,Luxiang Zou,Xiaohui Wei,Dongmei He
Synovial inflammation and cartilage degeneration are two crucial pathologic features in temporomandibular joint osteoarthritis (TMJ OA). Cartilage repair can be very thorny in inflammatory environment, which is highly associated with the activated macrophages. Thus, simultaneous inflammation suppression and cartilage repair are strongly required. However, the clinically used intra-articular injection agents face the problems of insufficient inflammation suppression, deficient cartilage repair and non-targeted therapy. Hence, we developed the novel dual-targeted lipid nanoparticles (LNPs) loaded with miR-330-3p, an important inflammation inhibitor, and kartogenin (KGN), a pro-chondrogenic small molecular, for synergistic anti-inflammation and cartilage repair of TMJ OA. The folic acid (FA) and collagen II-targeting peptide (WYRGRL) were modified on the surface of LNPs for precise delivery to macrophages or chondrocytes, respectively. The dual-targeted miR-330-3p@FA-LNP and KGN@WYRGRL-LNP both manifested high bioavailability and selectively active cellular uptake. Furthermore, it functioned synergistically to alleviate synovium inflammation and cartilage degeneration via modulating the M1 to M2 repolarization of macrophages and maintaining the homeostasis of chondrocytes, with a low intra-articular injection dose of miR-330-3p@FA-LNP (0.0125 nmol) and KGN@W-LNP (0.025 nmol) in vivo. RNA-seq and further validation demonstrated that miR-330-3p functioned by inhibiting SPARC and KGN functioned by upregulating EPHB4. In summary, this dual-targeted LNPs system provides a promising therapeutic strategy for TMJ OA treatment.
研究领域:
纳米技术
·
药理学
·
骨科
·
炎症
·
软骨生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）