Delivery of miR-212 by chimeric peptide-condensed supramolecular nanoparticles enhances the sensitivity of pancreatic ductal adenocarcinoma to doxorubicin

Chen, Wei; Zhou, Yue; Zhi, Xu; Ma, Tao; Líu, Hao; Chen, Brayant Wei; Zheng, Xiaoxiao; Xie, Shangzhi; Zhao, Bin; Feng, Xin‐Hua; Dang, Xiaowei; Liang, Tingbo

doi:10.1016/j.biomaterials.2018.11.035

Cited by 64 publications

(35 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, extensive studies in vivo focused on the role of miR-212-5p in tumor pathogenesis [68,69], lipid metabolism [70,71] and endocrine signaling axis [72,73], while very limited data reported in nervous system. Sun et al reported that miR-212-5p could attenuate damage and loss of dopaminergic neuron in the mouse model of Parkinson's disease [67]; Smith and the colleagues reported that miR-132/212 knockout mice have impaired memory while treatment with miR-132 rescues the memory deficits by reducing the phosphorylated tau [24].…”

Section: Discussionmentioning

confidence: 99%

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

et al. 2019

View full text Add to dashboard Cite

Ferroptosis, a newly discovered form of iron-dependent regulated cell death, has been implicated in traumatic brain injury (TBI). MiR-212-5p has previously been reported to be downregulated in extracellular vesicles following TBI. To investigate whether miR-212-5p is involved in the ferroptotic neuronal death in TBI mice, we first examined the accumulation of malondialdehyde (MDA) and ferrous ion, and the expression of ferroptosis-related molecules at 6 h, 12 h, 24 h, 48 h and 72 h following controlled cortical impact (CCI) in mice. There was a significant upregulation in the expression of Gpx4 and Acsl4 at 6 h, Slc7a11 from 12 h to 72 h, and Nox2 and Sat1 from 6 h to 72 h post injury. Similarly, an upregulation in the expression of Gpx4 at 6 h, Nox2 from 6 h to 72 h, xCT from 12 h to 72 h, and Sat1 at 72 h after CCI was observed at the protein level. Interestingly, MDA and ferrous ion were increased whereas miR-212-5p was decreased in the CCI group compared to the sham group. Furthermore, we found that overexpression of miR-212-5p attenuated ferroptosis while downregulation of miR-212-5p promoted ferroptotic cell death partially by targeting prostaglandin-endoperoxide synthase-2 (Ptgs2) in HT-22 and Neuro-2a cell lines. In addition, administration of miR-212-5p in CCI mice significantly improved learning and spatial memory. Collectively, these findings indicate that miR-212-5p may protect against ferroptotic neuronal death in CCI mice partially by targeting Ptgs2.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Autophagy is a highly conserved catabolic process induced by various cellular stresses including energy or nutrient shortage and cytotoxic insults, and performs the primary functions of cellular self-protection and adaptation to the changing environment 7 . Doxorubicin treatment induces autophagy which contributes to the development of chemoresistance, and inhibition of autophagy effectively overcomes or reverses doxorubicin resistance in a variety of cancers 8–10 . Although a number of autophagy-targeted interventions such as Lys05, HSF1/ATG4B knockdown, and ADCX have been reported to sensitize HCC cells to doxorubicin 11–13 , clinically beneficial autophagy modulations against doxorubicin resistance in HCC patients are still rare and need further exploration.…”

Section: Introductionmentioning

confidence: 99%

miR-223 overexpression inhibits doxorubicin-induced autophagy by targeting FOXO3a and reverses chemoresistance in hepatocellular carcinoma cells

et al. 2019

Self Cite

View full text Add to dashboard Cite

Doxorubicin is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. Autophagy, a conserved catabolic process for cellular self-protection and adaptation to the changing environment, is regarded as a potential clinical target to overcome doxorubicin resistance. In this study, the potential role of miR-223 in modulating doxorubicin-induced autophagy and sensitivity were evaluated in four transfected human HCC cell lines, and the in vivo relevance was assessed using a mouse xenograft model of HCC. We found that the well-defined miR-223 is expressed at low levels in doxorubicin treated HCC cells and that miR-223 overexpression inhibits the doxorubicin-induced autophagy that contributes to chemoresistance. Blockade of autophagic flux by chloroquine resulted in the failure of miR-223 inhibitor to suppress doxorubicin sensitivity of HCC cells. We further identified FOXO3a as a direct downstream target of miR-223 and primary mediator of the regulatory effect of miR-223 on doxorubicin-induced autophagy and chemoresistance in HCC cells. Finally, we confirmed the enhancement of doxorubicin sensitivity by agomiR-223 in xenograft models of HCC. These findings establish a novel miRNA-based approach for autophagy interference to reverse doxorubicin resistance in future chemotherapy regimens against human HCC.

show abstract

“…PC is considered as the most devastating malignancies known to man, characterized by rarely exhibiting symptoms at the early stage, poor prognosis, rapid growth, and expansion [25]. Hence, a comprehensive understanding of the molecular mechanisms associated with the physiology of PC is urgently required.…”

Section: Discussionmentioning

confidence: 99%

Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway

et al. 2020

View full text Add to dashboard Cite

Background: Recent studies have emphasized determining the ability of microRNAs (miRNAs) as crucial regulators in the occurrence and development of pancreatic cancer (PC), which continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-135b and its associated mechanism to unravel the biological characteristics of tumor growth in pancreatic cancer stem cells (PCSCs). Methods: Microarray analyses were initially performed to identify the PC-related miRNAs and genes. The expression of miR-135b and PCSC markers in PC tissues and cells was determined by RT-qPCR and western blot analysis, respectively. The potential gene (JADE-1) that could bind to miR-135b was confirmed by the dual-luciferase reporter assay. To investigate the tumorigenicity, migration, invasion, and stemness of PC cells, several gain-of-function and loss-offunction genetic experiments were conducted. Finally, tumor formation in nude mice was conducted to confirm the results in vivo. Results: miR-135b was highly-expressed in PC tissues and PCSCs, which was identified to specifically target JADE-1. The overexpression of miR-135b promoted proliferation, migration, and invasion of PCSC, inhibited cell apoptosis and increased the expression of stemness-related factors (Sox-2, Oct-4, Nanog, Aldh1, and Slug). Moreover, miR-135b could promote the expression of phosphorylated AKT and phosphorylated mTOR in the AKT/mTOR pathway. Additionally, miR-135b overexpression accelerated tumor growth in nude mice. Conclusions: Taken together, the silencing of miR-135b promotes the JADE-1 expression, which inactivates the AKT/mTOR pathway and ultimately results in inhibition of self-renewal and tumor growth of PCSCs. Hence, this study contributes to understanding the role of miR-135 in PCSCs and its underlying molecular mechanisms to aid in the development of effective PC therapeutics.

show abstract

Delivery of miR-212 by chimeric peptide-condensed supramolecular nanoparticles enhances the sensitivity of pancreatic ductal adenocarcinoma to doxorubicin

Cited by 64 publications

References 43 publications

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

miR-223 overexpression inhibits doxorubicin-induced autophagy by targeting FOXO3a and reverses chemoresistance in hepatocellular carcinoma cells

Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway

Contact Info

Product

Resources

About