Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells

Kang, Le; Hao, Jia; Huang, Bingqing; Lu, Shuyang; Chen, Zhongzhou; Shen, Jie; Zou, Yunzeng; Wang, Chunsheng; Sun, Yongxin

doi:10.3389/fgene.2021.596169

Cited by 25 publications

(17 citation statements)

References 33 publications

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“…The causal relationship between ALDH2 and stroke still need further study. CDK6 has been identified as a key regulator of atherosclerosis for CDK6 knockdown can suppress proliferation of HASMC and HUASMC [ 40 ]. A previous study has also shown the down-regulation of CDK6 in the penumbra surrounding the infarction region comparing with control [ 41 ], which supports the inverse association between expression of CDK6 and the risk of AS and AIS in our TWAS analysis.…”

Section: Discussionmentioning

confidence: 99%

Identifying causal genes for stroke via integrating the proteome and transcriptome from brain and blood

Chen

Huang

et al. 2022

J Transl Med

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Background Genome-wide association studies (GWAS) have revealed numerous loci associated with stroke. However, the underlying mechanisms at these loci in the pathogenesis of stroke and effective stroke drug targets are elusive. Therefore, we aimed to identify causal genes in the pathogenesis of stroke and its subtypes. Methods Utilizing multidimensional high-throughput data generated, we integrated proteome-wide association study (PWAS), transcriptome-wide association study (TWAS), Mendelian randomization (MR), and Bayesian colocalization analysis to prioritize genes that contribute to stroke and its subtypes risk via affecting their expression and protein abundance in brain and blood. Results Our integrative analysis revealed that ICA1L was associated with small-vessel stroke (SVS), according to robust evidence at both protein and transcriptional levels based on brain-derived data. We also identified NBEAL1 that was causally related to SVS via its cis-regulated brain expression level. In blood, we identified 5 genes (MMP12, SCARF1, ABO, F11, and CKAP2) that had causal relationships with stroke and stroke subtypes. Conclusions Together, via using an integrative analysis to deal with multidimensional data, we prioritized causal genes in the pathogenesis of SVS, which offered hints for future biological and therapeutic studies.

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Section: Discussionmentioning

confidence: 99%

Identifying causal genes for stroke via integrating the proteome and transcriptome from brain and blood

Chen

Huang

et al. 2022

J Transl Med

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“…Moreover, highly expressed miR-375-3p significantly reduced the mRNA levels of MYOCD and downstream contracted proteins. Phenotypic transformation of VSMCs plays an important role in cardiovascular disease [ 33 ]. The transformation of VSMCs from contractile type to synthetic type is often accompanied by the enhancement of cell proliferation and migration ability and the increase of pro-inflammatory cytokines secretion, which leads to a series of vascular diseases [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375-3p is implicated in carotid artery stenosis by promoting the cell proliferation and migration of vascular smooth muscle cells

Yin

Cheng

et al. 2021

BMC Cardiovasc Disord

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Background Atherosclerosis is the main cause of carotid artery stenosis (CAS) which mostly occurs in the elderly. In this paper, the expression level of miR-375-3p in asymptomatic CAS patients and its diagnostic value for asymptomatic CAS were investigated, and the effects of miR-375-3p on the cell proliferation and migration of vascular smooth muscle cells (VSMCs) was further explored. Methods 98 healthy subjects and 101 asymptomatic CAS patients were participated in this study. qRT-PCR was used to measure the expression level of serum miR-375-3p, and the ROC curve was established to evaluate the predictive value of miR-375-3p for asymptomatic CAS. After transfection with miR-375-3p mimic or inhibitor in vitro, cell proliferation and migration were detected by CCK-8 assay, colony formation assay, and Transwell assay, respectively. The levels of TNF-α, IL-1β, IL-6 were detected by ELISA. Western blot was used to detect the protein expression of XIAP. Finally, luciferase reporter gene assay was applied to assess the interaction of miR-375-3p with target genes. Results The expression level of serum miR-375-3p in asymptomatic CAS patients was significantly higher than that in healthy controls, and the AUC value of ROC curve was 0.888. The sensitivity and specificity were 80.2 and 86.7%, respectively, indicating that miR-375-3p had high diagnostic value for asymptomatic CAS. In vitro cell experiments showed that up-regulation of miR-375-3p significantly promoted the proliferation and migration of VSMCs, and also promoted the generation of inflammatory factors and phenotypic transformation of VSMCs. Luciferase reporter gene assay confirmed that XIAP was a target gene of miR-375-3p and was negatively regulated by miR-375-3p. Conclusions In this study, miR-375-3p may have a clinical diagnostic value for asymptomatic CAS patients which need further validation. Increased miR-375-3p levels in CAS may be associated with increased proliferation and migration of VSMCs via downregulation of the apoptosis inducing gene XIAP.

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“…In cancer and other diseases, various circRNAs can inhibit the expression of miR-637. These circR-NAs include circHIPK3 (CRC [6], CHOL [73], and atherosclerosis [74]), circEPHB4(GBM/LGG) [8], circ_0001947(NSCLC) [75], circ_0080145(CML) [34], circ_0051886(CML) [34], circUSP36(atherosclerosis) [76], and circUBR4(atherosclerosis) [77].…”

Section: The Mir-637-related Cernasmentioning

confidence: 99%

Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis

Shen

Liang

et al. 2022

Biomark Res

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MicroRNAs (miRNAs) are a class of small non-coding RNAs ranging from 17 to 25 nt in length. miR-637 is down-regulated in most cancers and up-regulated only in clear cell renal cell carcinoma (ccRCC). miR-637 can target 21 protein-coding genes, which are involved in the regulation of cell growth, cell cycle, cell proliferation, epithelial-mesenchymal transition (EMT), cancer cell invasion and metastasis, etc. In glioma, the transcription factor ZEB2 can bind to the miR-637 promoter region and inhibit miR-637 expression. Besides, miR-637 could be negatively regulated by competing endogenous RNA (ceRNAs) comprising 13 circular RNA (circRNAs) and 9 long non-coding RNA (lncRNAs). miR-637 is involved in regulating five signaling pathways, including the Jak/STAT3, Wnt/β-catenin, PI3K/AKT, and ERK signaling pathways. Low miR-637 expression was significantly associated with larger tumors and later tumor node metastasis (TNM) staging in cancer patients. Low miR-637 expression was also associated with poorer overall survival (OS) in cancer patients such as glioblastoma and low-grade gliomas (GBM/LGG), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian cancer (OV). Low expression of miR-637 increases the resistance of colorectal cancer (CRC) and human cholangiocarcinoma (CHOL) cancer cells to three anticancer chemotherapeutics (gemcitabine (dFdC), cisplatin (DDP), and oxaliplatin (OXA)). Our work summarizes the abnormal expression of miR-637 in various cancers, expounds on the ceRNA regulatory network and signaling pathway involved in miR-637, and summarizes the effect of its abnormal expression on the biological behavior of tumor cells. At the same time, the relationship between the expression levels of miR-637 and its related molecules and the prognosis and pathological characteristics of patients was further summarized. Finally, our work points out the insufficiency of miR-637 in current studies and is expected to provide potential clues for future miR-637-related studies.

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Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells

Cited by 25 publications

References 33 publications

Identifying causal genes for stroke via integrating the proteome and transcriptome from brain and blood

Identifying causal genes for stroke via integrating the proteome and transcriptome from brain and blood

MicroRNA-375-3p is implicated in carotid artery stenosis by promoting the cell proliferation and migration of vascular smooth muscle cells

Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis

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