Prediction of MiR-21-5p in Promoting the Development of Lung Adenocarcinoma via PDZD2 Regulation

Cui, Shengjin; Lou, Shuang; Guo, Weiquan; Jian, Shihui; Wu, Yunfeng; Liu, Xintong; Lan, Xi; Jia, Xingwang

doi:10.12659/msm.923366

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…Plenty of studies have proven that miR-21 participates in the occurrence and development of tumors [ 79 , 80 ], cardiovascular [ 81 ] and lung diseases [ 82 , 83 ], glaucoma intraocular pressure [ 84 ], age-related skin wound healing [ 85 ], sepsis, and acute kidney injury [ 86 ]. Moreover, it is expected to be a potential marker for the diagnosis of diseases, such as colon cancer [ 87 ], liver cancer or hepatitis severity [ 88 ], colorectal cancer [ 89 ], and lung adenocarcinoma [ 90 ]. The expression of miR-21 was significantly elevated at 1, 4, 7, and 14 days after PNI and was able to regulate the gene expression of the sciatic nerve stump [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Liu

Yang

Mou

et al. 2022

Oxidative Medicine and Cellular Longevity

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Purpose. Our study is aimed at investigating the mechanism by which electroacupuncture (EA) promoted nerve regeneration by regulating the release of exosomes and exosome-mediated miRNA-21 (miR-21) transmission. Furthermore, the effects of Schwann cells- (SC-) derived exosomes on the overexpression of miR-21 for the treatment of PNI were investigated. Methods. A sciatic nerve injury model of rat was constructed, and the expression of miR-21 in serum exosomes and damaged local nerves was detected using RT-qPCR after EA treatment. The exosomes were identified under a transmission electron microscope and using western blotting analysis. Then, the exosome release inhibitor, GW4869, and the miR-21-5p-sponge used for the knockdown of miR-21 were used to clarify the effects of exosomal miR-21 on nerve regeneration promoted by EA. The nerve conduction velocity recovery rate, sciatic nerve function index, and wet weight ratio of gastrocnemius muscle were determined to evaluate sciatic nerve function recovery. SC proliferation and the level of neurotrophic factors were assessed using immunofluorescence staining, and the expression levels of SPRY2 and miR-21 were detected using RT-qPCR analysis. Subsequently, the transmission of exosomal miR-21 from SC to the axon was verified in vitro. Finally, the exosomes derived from the SC infected with the miR-21 overexpression lentivirus were collected and used to treat the rat SNI model to explore the therapeutic role of SC-derived exosomes overexpressing miR-21. Results. We found that EA inhibited the release of serum exosomal miR-21 in a PNI model of rats during the early stage of PNI, while it promoted its release during later stages. EA enhanced the accumulation of miR-21 in the injured nerve and effectively promoted the recovery of nerve function after PNI. The treatment effect of EA was attenuated when the release of circulating exosomes was inhibited or when miR-21 was downregulated in local injury tissue via the miR-21-5p-sponge. Normal exosomes secreted by SC exhibited the ability to promote the recovery of nerve function, while the overexpression of miR-21 enhanced the effects of the exosomes. In addition, exosomal miR-21 secreted by SC could promote neurite outgrowth in vitro. Conclusion. Our results demonstrated the mechanism of EA on PNI from the perspective of exosome-mediated miR-21 transport and provided a theoretical basis for the use of exosomal miR-21 as a novel strategy for the treatment of PNI.

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Section: Discussionmentioning

confidence: 99%

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Liu

Yang

Mou

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Previous studies have suggested that PDZD2 is an oncogene, which is over-expressed in the cell lines of osteosarcoma, human primary prostate tumor and prostate tumor ( He et al, 2019 ). Recently, it has been shown that human secreted PDZD2 (sPDZD2) has anti-tumor properties, and it is also down-regulated in lung adenocarcinoma ( Cui et al, 2020 ). Spdzd2 induces the aging of prostate cancer cells through mutation or transcriptional activation of wild-type p53, and makes cancer cells more sensitive to apoptosis through genotoxic stress ( Tam et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Biomarkers and Small Molecule Drugs for Cutaneous Melanoma Using Integrated Bioinformatic Analysis

Liu

Sun

Han

et al. 2022

Front. Cell Dev. Biol.

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Background: Cutaneous melanoma (CM) is a type of skin cancer with a high fatality rate, and its pathogenesis has not yet been fully elucidated.Methods: We obtained the gene expression datasets of CM through the Gene Expression Omnibus (GEO) database. Subsequently, robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between CM cases and normal skin controls. Gene functional annotation was performed to explore the potential function of the DEGs. We built the protein–protein interaction (PPI) network by the Interactive Gene database retrieval tool (STRING) and selected hub modules by Molecular Complexity Detection (MCODE). We furthered and validated our results using the TCGA-GTEX dataset. Finally, potential small molecule drugs were predicted by CMap database and verified by molecular docking method.Results: A total of 135 DEGs were obtained by RRA synthesis analysis. GMPR, EMP3, SLC45A2, PDZD2, NPY1R, DLG5 and ADH1B were screened as potential targets for CM. Furazolidone was screened as a potential small molecule drug for the treatment of CM, and its mechanism may be related to the inhibition of CM cell proliferation by acting on GMPR.Conclusion: We identified seven prognostic therapeutic targets associated with CM and furazolidone could be used as a potential drug for CM treatment, providing new prognostic markers, potential therapeutic targets and small molecule drugs for the treatment and prevention of CM.

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“…Despite intense research, 15,[17][18][19][20][21][22][23] understanding the binding of PDZD2 has remained elusive. In fact, notwithstanding its pivotal role in several types of cancers, no clear-cut evidence has been provided to univocally identify a physiological binding partner.…”

Section: The Binding Properties Of Spdzd2: a Cryptic Binding Activity...mentioning

confidence: 99%

“…The proteolytic processing by caspase of PDZD2 produces a secreted form of PDZD2 (sPDZD2), which acts as a signaling molecule and consists of a tandem of two PDZ domains namely PDZ5 and PDZ6 16 . Several studies have shown that sPDZD2 is unregulated in several types of cancers 15,17–21 . Despite its importance, a specific ligand of sPDZD2 has not been directly identified; although previous studies in cellula have suggested an interaction with the C‐terminal tail of the D4 immunoglobulin‐like domain of the CD4 co‐receptor 22,23 …”

Section: Introductionmentioning

confidence: 99%

“…16 Several studies have shown that sPDZD2 is unregulated in several types of cancers. 15,[17][18][19][20][21] Despite its importance, a specific ligand of sPDZD2 has not been directly identified; although previous studies in cellula have suggested an interaction with the C-terminal tail of the D4 immunoglobulin-like domain of the CD4 co-receptor. 22,23 To shed light on the stability and function of sPDZD2, we investigated its pathway of folding and unfolding.…”

Section: Introductionmentioning

confidence: 99%

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Cryptic binding properties of a transient folding intermediate in a PDZ tandem repeat

et al. 2022

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PDZ domains are the most diffused protein–protein interaction modules of the human proteome and are often present in tandem repeats. An example is PDZD2, a protein characterized by the presence of six PDZ domains that undergoes a proteolytic cleavage producing sPDZD2, comprising a tandem of two PDZ domains, namely PDZ5 and PDZ6. Albeit the physiopathological importance of sPDZD2 is well‐established, the interaction with endogenous ligands has been poorly characterized. To understand the determinants of the stability and function of sPDZD2, we investigated its folding pathway. Our data highlights the presence of a complex scenario involving a transiently populated folding intermediate that may be accumulated from the concurrent denaturation of both PDZ5 and PDZ6 domains. Importantly, double jump kinetic experiments allowed us to pinpoint the ability of this transient intermediate to bind the physiological ligand of sPDZD2 with increased affinity compared to the native state. In summary, our results provide an interesting example of a functionally competent misfolded intermediate, which may exert a cryptic function that is not captured from the analysis of the native state only.

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Prediction of MiR-21-5p in Promoting the Development of Lung Adenocarcinoma via PDZD2 Regulation

Cited by 6 publications

References 28 publications

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

Identification of Potential Biomarkers and Small Molecule Drugs for Cutaneous Melanoma Using Integrated Bioinformatic Analysis

Cryptic binding properties of a transient folding intermediate in a PDZ tandem repeat

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