lncRNA/circRNA‑miRNA‑mRNA ceRNA network in lumbar intervertebral disc degeneration

Zhu, Jinwen; Zhang, Chi; Gao, Wenjie; Hu, Huimin; Wang, Xiaodong; Hao, Dingjun

doi:10.3892/mmr.2019.10569

Cited by 94 publications

(113 citation statements)

References 58 publications

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“…Our results found miR-4450 was significantly up-regulated in IDD, which highlights its possible role in the pathogenesis of IDD, and the inhibition of miR-4450 may help protect NP. Two other studies further confirmed this trend [25,26]. Therefore, the overexpression of miR-4450 in NP of IDD patients highlights its possible role in the pathogenesis of IDD, and the inhibition of miR-4450 may help protect NP.…”

Section: Discussionmentioning

confidence: 65%

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

Yuan

Wang

Liu

et al. 2020

Preprint

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Background Exosomes derived from mesenchymal stem cells (MSCs) have emerged as novel drug and gene delivery tools. Current study aimed to elucidate the potential therapeutic role of human placental MSC (hPLMSC)-derived exosomes carrying antagomiR-4450 (EXO-antagomiR-4450) in intervertebral disc degeneration (IDD) progression. Methods Initially, the differentially expressed miRNAs related to IDD were identified by microarray analysis which provided data predicting the interaction between miR-4450 and ZNF121 in IDD. Next, miR-4450 and ZNF121 were elevated or silenced to determine their effects on the damage of NPCs treated with TNF-α. The therapeutic effects of EXO-antagomiR-4450 on nucleus pulposus cells (NPCs) were verified both in vitro and in vivo, especially gait analysis and fluorescent molecular tomopraphy were used in live IDD mice. Results Our results revealed that miR-4450 was highly expressed, while ZNF121 was poorly expressed in IDD patients and NPCs treated with TNF-α. Furthermore, miR-4450 was identified to specifically target ZNF121. Additionally, the inhibition of miR-4450 exerted an alleviatory effect on the inflammation, apoptosis and damage of the NPCs by up-regulating ZNF121. Moreover, EXO-antagomiR-4450 retarded damage of NPCs in vitro, alleviated IDD damage and ameliorated gait abnormality in vivo. Conclusion hPLMSC-derived exosomes could be a feasible nanovehicle to deliver inhibitory oligonucleotides like antagomiR-4450 in IDD.

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Section: Discussionmentioning

confidence: 65%

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

Yuan

Wang

Liu

et al. 2020

Preprint

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“…Emerging evidences indicated that circRNAs sponged miRNAs to exert their biological functions [19][20][21], and hsa_circRNA_103809 facilitated cancer progressions by regulating miRNAs in a competing endogenous RNA (ceRNA)-dependent manner [14,[16][17][18]22]. By searching the online Pubmed database (https://pubmed.ncbi.nlm.nih.gov/), the miRNAs, including miR-101-3p [17], miR-532-3p [14], miR-4302 [18], miR-620 [22] and miR-377-3p [16], could be sponged by hsa_circRNA_103809.…”

Section: Discussionmentioning

confidence: 99%

“…According to our recent advances in circRNAs research, circRNAs exerted their biological functions and regulated genes expression through serving as RNA sponges to competitively bind to microRNAs (miRNAs) [19][20][21]. Taken hsa_circRNA_103809 as an example, previous publications indicated that hsa_circRNA_103809 sponged multiple RNAs, including miR-101-3p [17], miR-532-3p [14], miR-4302 [18], miR-620 [22] and miR-377-3p [16].…”

Section: Introductionmentioning

confidence: 99%

A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC)

Zhu

Han

Lan

et al. 2020

Preprint

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Background Cisplatin is the first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), and emerging evidences suggests that targeting circular RNAs (circRNAs) is an effective strategy to increase cisplatin-sensitivity in NSCLC, but the detailed mechanisms are still not fully delineated. Methods Cell proliferation, viability and apoptosis were examined by using the cell counting kit-8 (CCK-8) assay, trypan blue staining assay and Annexin V-FITC/PI double staining assay, respectively. The expression levels of cancer associated genes were measured by using the Real-Time qPCR and Western Blot analysis at transcriptional and translated levels. Dual-luciferase reporter gene system assay was conducted to validated the targeting sites among hsa_circRNA_103809, miR-377-3p and 3’ untranslated region (3’UTR) of GOT1 mRNA. The expression status, including expression levels and localization, were determined by immunohistochemistry (IHC) assay in mice tumor tissues. Results Here we identified a novel hsa_circRNA_103809/miR-377-3p/GOT1 signaling cascade contributes to cisplatin-resistance in NSCLC in vitro and in vivo. Mechanistically, parental cisplatin-sensitive NSCLC (CS-NSCLC) cells were subjected to continuous low-dose cisplatin treatment to generate cisplatin-resistant NSCLC (CR-NSCLC) cells, and we found that hsa_circRNA_103809 and GOT1 were upregulated, while miR-377-3p was downregulated in CR-NSCLC cells but not in CS-NSCLC cells. In addition, hsa_circRNA_103809 sponged miR-337-3p to upregulate GOT1 in CS-NSCLC cells, and knock-down of hsa_circRNA_103809 enhanced the inhibiting effects of cisplatin on cell proliferation and viability, and induced cell apoptosis in CR-NSCLC cells, which were reversed by downregulating miR-377-3p and overexpressing GOT1. Consistently, overexpression of hsa_circRNA_103809 increased cisplatin-resistance in CS-NSCLC cells by regulating the miR-377-3p/GOT1 axis. Finally, silencing of hsa_circRNA_103809 aggravated the inhibiting effects of cisplatin treatment on NSCLC cell growth in vivo. Conclusions Analysis of data suggested that targeting the hsa_circRNA_103809/miR-377-3p/GOT1 pathway increased susceptibility of CR-NSCLC cells to cisplatin, and this study provided novel targets to improve the therapeutic efficacy of cisplatin for NSCLC treatment in clinic.

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“…Non-coding RNAs, which can regulate gene expression, are involved in many pathophysiological processes in intervertebral disc cells (6,7). MiRNA is a small, short-stranded fraction of lncRNA that binds to the 3'UTR of the target gene mRNA to inhibit mRNA translation or induce its degradation, thus regulating cell differentiation, proliferation, and survival (8).…”

Section: Introductionmentioning

confidence: 99%

MiR-25 Protects Against Apoptosis of Nucleus Pulposus Cells by Targeting SUMO2 in Intervertebral Disc Degeneration

Lei

Li²,

Guang³

et al. 2020

Preprint

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Background MiR-25 was reported to be down-regulated in patients with intervertebral disc degeneration (IDD). However, the potential role of miR-25 in IDD remained unclear. Therefore, the present study aimed to investigate the effects of miR-25 on human intervertebral disc nucleus pulposus cells (NPCs).Methods We evaluated the expression of miR-25 and small ubiquitin-related modifier 2 (SUMO2) in human nucleus pulposus (NP) tissues by real-time PCR and western blotting. Then, the target relationship between miR-25 and SUMO2 was validated by luciferase reporter assay and biotin-coupled miRNA pulldown assay. The potential roles of miR-25 in NPC proliferation and apoptosis were confirmed using CCK-8 assay, EdU incorporation assay, and flow cytometry.Results MiR-25 was lowly expressed in the patients with IDD. In addition, miR-25 facilitated the growth of NPCs by increasing cell proliferation and inhibiting apoptosis. Furthermore, we elucidated that SUMO2 was a target gene of miR-25, and was regulated by miR-25 through p53 signaling pathway. Restore of SUMO2 expression abrogated the effects of miR-25 on NPCs.Conclusion MiR-25 promoted the proliferation, inhibited the apoptosis of NPCs, and suppressed the development of IDD via SUMO2-mediated p53 signaling axis.

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lncRNA/circRNA‑miRNA‑mRNA ceRNA network in lumbar intervertebral disc degeneration

Cited by 94 publications

References 58 publications

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC)

MiR-25 Protects Against Apoptosis of Nucleus Pulposus Cells by Targeting SUMO2 in Intervertebral Disc Degeneration

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