MicroRNA-21-5p Reduces Hypoxia/Reoxygenation-Induced Neuronal Cell Damage through Negative Regulation of CPEB3

Objectives. To explore the role of microRNA-21-5p (miR-21-5p) in hypoxia/reoxygenation- (H/R-) induced HT22 cell damage. Methods. The hypoxia/reoxygenation (H/R) model was established in mouse neuronal cells HT22. Cell Counting Kit-8 (CCK-8) and qRT-PCR were used to determine the effects of H/R treatment on cell viability and miR-21-5p expression. HT22 cells were transfected with miR-21-5p mimic or negative control (NC) followed by the induction of H/R; cell viability, apoptosis, and SOD, MDA, and LDH activities were detected. Besides, the apoptosis-related proteins including BAX, BCL2, cleaved caspase-3, and caspase-3 as well as proteins of EGFR/PI3K/AKT signaling pathways were measured by Western blot. To verify the target relation between cytoplasmic polyadenylation element binding protein 3 (CPEB3) and miR-21-5p, luciferase reporter gene experiment was performed. After cotransfection with miR-21-5p mimic and CPEB3 plasmids, the reversal effects of CPEB3 on miR-21-5p in H/R damage were studied. Results. H/R treatment could significantly reduce the cell viability ( P < 0.05 ) and miR-21-5p levels ( P < 0.05 ) in HT22 cells. After overexpressing miR-21-5p, cell viability was increased ( P < 0.05 ) under H/R treatment, and the apoptosis rate and the levels of apoptosis-related proteins were suppressed (all P < 0.05 ). Furthermore, SOD activity was increased ( P < 0.05 ), while MDA and LDH activity was decreased (both P < 0.05 ). Besides, miR-21-5p could restore the activation of the EGFR/PI3K/AKT signaling pathway inhibited by H/R treatment (all P < 0.05 ). The luciferase reporter gene experiment verified that CPEB3 is the target of miR-21-5p ( P < 0.05 ). When coexpressing miR-21-5p mimic and CPEB3 in the cells, the protective effects of miR-21-5p under H/R were reversed (all P < 0.05 ), and the activation of the EGFR/PI3K/AKT pathway was also inhibited (all P < 0.05 ). Conclusion. This study showed that miR-21-5p may regulate the EGFR/PI3K/AKT signaling pathway by targeting CPEB3 to reduce H/R-induced cell damage and apoptosis.

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MiR-486 protects against acute myocardial infarction via regulation of PTEN

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i9.10 ◽

2021 ◽

Vol 20 (9) ◽

pp. 1845-1853

Author(s):

Qinfeng Han ◽

Zhong Xu ◽

Xiaolei Zhang ◽

Kun Yang ◽

Zhifei Sun ◽

...

Keyword(s):

Myocardial Infarction ◽

Akt Signaling ◽

Reporter Gene Assay ◽

Expression Level ◽

Luciferase Reporter ◽

Akt Signaling Pathway ◽

Luciferase Reporter Gene ◽

Luciferase Reporter Gene Assay ◽

Qrt Pcr ◽

Gene Assay

Purpose: To investigate the effect of miR-486 on rats with acute myocardial infarction (AMI), and its mechanism of action.Methods: A rat model of AMI was established. They were randomly divided into 4 groups, namely, sham, model, agomiR-486 and antagomiR-486 groups, respectively. Rats in these different groups were treated with agomiR-21 (5 μL, 40 nmol/mL), antagomiR-21 (5 μL, 40 nmol/mL) or agomiR-NC (5 μL, 40 nmol/mL), respectively. Then, key miRNAs were sorted out using gene-chip assay and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Luciferase reporter gene assay was conducted to determine the interaction between miR-486 and gene of PTEN. After intraperitoneal injection of agomiR-486 and antagomiR-486, hemodynamics was measured to determine the effect of miR-486 on myocardial function of the rats. The effect of miR-486 expression level on the expression of myocardial enzymes in serum, the morphology of myocardial tissues, and the apoptosis of myocardial tissues in rats, were investigated. Additionally, the effect of miR-486 expression level on PTEN/AKT signaling pathway in the rats was determined by Western blotting.Results: The results of gene-chip and qRT-PCR assays revealed that there were 8 differentially expressed genes in rat myocardial tissues in the model group when compared with the sham group. MiR-486 improved the cardiac function of rats and the morphology of myocardial tissues, but reduced AMI-induced apoptosis of myocardial cells and the expression of myocardial enzymes (markers of myocardial injury) in a dose-dependent manner (p < 0.05). The results of luciferase reporter gene assay showed that PTEN was a direct target of miR-486. In rat models of AMI, a raised expression of miR-486 remarkably suppressed the protein expression level of PTEN and up-regulated that of p-AKT/AKT (p < 0.05).Conclusion: MiR-486 protects against AMI in rats probably by targeting PTEN and activating the AKT signaling pathway. The results of the current study may provide new insights for the treatment of AMI.

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Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma

AJP Cell Physiology ◽

10.1152/ajpcell.00324.2017 ◽

2018 ◽

Vol 315 (6) ◽

pp. C839-C849 ◽

Cited By ~ 10

Author(s):

Xin-Gang Nie ◽

Dong-Sheng Fan ◽

Yan-Xia Huang ◽

Ying-Ying He ◽

Bo-Li Dong ◽

...

Keyword(s):

Signaling Pathway ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Akt Signaling ◽

Luciferase Reporter ◽

Ultrastructural Changes ◽

Retinal Ganglion ◽

Akt Signaling Pathway ◽

Luciferase Reporter Gene ◽

Gene Assay

Glaucoma represents a major cause of blindness, generally associated with elevated intraocular pressure (EIOP). The aim of the present study was to investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs) and the underlying mechanism based on a mouse model of chronic glaucoma with EIOP. The successfully modeled mice were administered with mimics or inhibitors of miR-149. Next, the number of RGCs, ultrastructural changes of RGCs, and purity of RGCs in the retinal tissues were detected. Moreover, the RGCs were collected and subsequently treated with 60 mmHg pressure and transfected with a series of plasmids aiding in the regulation of the expression of miR-149 and betacellulin (BTC). The levels of miR-149, BTC, phosphatidylinositol 3-kinase (PI3K), and Akt were subsequently determined. Finally, RGC viability and apoptosis were detected accordingly. Dual luciferase reporter gene assay provided validation, highlighting BTC was indeed a target gene of miR-149. The downregulation of miR-149 is accompanied by an increased number of RGCs and decreased ultrastructural RGC alterations. Additionally, downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in both the retinal tissues and RGCs, whereas the silencing of miR-149 was observed to promote the viability of RGC and inhibit RGC apoptosis. Taken together, the results of the current study provided validation suggesting that the downregulation of miR-149 confers protection to RGCs by means of activating the PI3K/Akt signaling pathway via upregulation of BTC in mice with glaucoma. Evidence presented indicated the promise of miR-149 inhibition as a potential therapeutic strategy for glaucoma treatment.

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YY1 Activates EMI2 and Promotes the Progression of Cholangiocarcinoma Through the PI3K/Akt Signaling Axis

10.21203/rs.3.rs-792593/v1 ◽

2021 ◽

Author(s):

Shuai zhou ◽

Kang Lin Qu ◽

JinAng Li ◽

Shilei Chen ◽

Yi Gang Zhang ◽

...

Keyword(s):

Transcription Factors ◽

Bile Duct ◽

Signaling Pathway ◽

Akt Signaling ◽

Reporter Gene Assay ◽

Luciferase Reporter ◽

Akt Signaling Pathway ◽

Luciferase Reporter Gene ◽

Luciferase Reporter Gene Assay ◽

Gene Assay

Abstract Background: Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known.Methods: The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells.Results: EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and inhibition of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2.Conclusion: EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

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Knockdown of Tripartite Motif 8 Protects H9C2 Cells Against Hypoxia/Reoxygenation-Induced Injury Through the Activation of PI3K/Akt Signaling Pathway

Cell Transplantation ◽

10.1177/0963689720949247 ◽

2020 ◽

Vol 29 ◽

pp. 096368972094924

Author(s):

Xiaoyan Dang ◽

Yong Qin ◽

Changwei Gu ◽

Jiangli Sun ◽

Rui Zhang ◽

...

Keyword(s):

Cell Viability ◽

Signaling Pathway ◽

Ischemia Reperfusion ◽

Akt Signaling ◽

H9c2 Cells ◽

Loss Of Function ◽

Akt Signaling Pathway ◽

Tripartite Motif ◽

Myocardial Ischemia Reperfusion ◽

Hypoxia Reoxygenation

Tripartite motif 8 (TRIM8) is a member of the TRIM protein family that has been found to be implicated in cardiovascular disease. However, the role of TRIM8 in myocardial ischemia/reperfusion (I/R) has not been investigated. We aimed to explore the effect of TRIM8 on cardiomyocyte H9c2 cells exposed to hypoxia/reoxygenation (H/R). We found that TRIM8 expression was markedly upregulated in H9c2 cells after stimulation with H/R. Gain- and loss-of-function assays proved that TRIM8 knockdown improved cell viability of H/R-stimulated H9c2 cells. In addition, TRIM8 knockdown suppressed reactive oxygen species production and elevated the levels of superoxide dismutase and glutathione peroxidase. Knockdown of TRIM8 suppressed the caspase-3 activity, as well as caused significant increase in bcl-2 expression and decrease in bax expression. Furthermore, TRIM8 overexpression exhibited apposite effects with knockdown of TRIM8. Finally, knockdown of TRIM8 enhanced the activation of PI3K/Akt signaling pathway in H/R-stimulated H9c2 cells. Inhibition of PI3K/Akt by LY294002 reversed the effects of TRIM8 knockdown on cell viability, oxidative stress, and apoptosis of H9c2 cells. These present findings defined TRIM8 as a therapeutic target for attenuating and preventing myocardial I/R injury.

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miR-27b-3p Improved High Glucose-Induced Spermatogenic Cell Damage via Regulating Gfpt1/HBP Signaling

European Surgical Research ◽

10.1159/000518960 ◽

2022 ◽

pp. 1-13

Author(s):

Hong Zheng ◽

Jian Huang ◽

Ming Zhang ◽

Hu-Juan Zhao ◽

Pang Chen ◽

...

Keyword(s):

Cell Viability ◽

High Glucose ◽

Cell Damage ◽

Malonic Dialdehyde ◽

Spermatogenic Cell ◽

Luciferase Reporter ◽

Spermatogenic Cells ◽

Testicular Damage ◽

Hexosamine Biosynthetic Pathway ◽

Related Proteins

Introduction: Diabetes mellitus (DM)-induced testicular damage is characterized by abnormal apoptosis of spermatogenic cells. Here, we clarified the roles and the molecular mechanism of microRNA (miR)-27b-3p in high glucose (HG)-induced spermatogenic cell damage. Methods: GC-1 spg cells were treated with 30 mmol/L glucose for 24 h. Cell viability was assessed by 2.3 3-(4, 5-dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide (MTT) assay. And, levels of O-linked N-acetylglucosamine (OGT), apoptosis-related proteins, and autophagy-related proteins were evaluated using Western blot. Levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and UDP-N-acetylglucosamine (UDP-GlcNAc) were assessed by enzyme linked immunosorbent (ELISA) assay. Levels of reactive oxygen species (ROS), malonic dialdehyde (MDA) and activity of superoxide dismutase (SOD) in cells were determined using kits. Cell apoptosis was determined using flow cytometry assay. Besides, dual luciferase reporter assay was employed to verify the binding relationship between miR-27b-3p and glutamine-fructose-6-phosphate transaminase 1 (Gfpt1). Results: miR-27b-3p was markedly downregulated in HG-treated GC-1 spg cells. HG treatment caused decreased cell viability, increased oxidative stress and inflammation, and induced autophagy and apoptosis, which were abolished by miR-27b-3p overexpression. miR-27b-3p suppressed the activation of hexosamine biosynthetic pathway (HBP) signaling in HG-treated spermatogenic cells. miR-27b-3p directly bound to Gfpt1 and negatively regulated its expression. Conclusion: miR-27b-3p could improve HG-induced spermatogenic cell damage via regulating Gfpt1/HBP signaling, providing a new treatment strategy for the treatment of DM-induced testicular damage.

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Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.626027 ◽

2021 ◽

Vol 9 ◽

Author(s):

Wenchang Lv ◽

Shengxuan Liu ◽

Qi Zhang ◽

Weijie Hu ◽

Yiping Wu ◽

...

Keyword(s):

Extracellular Matrix ◽

Signaling Pathway ◽

Therapeutic Potential ◽

Akt Signaling ◽

Luciferase Reporter ◽

Akt Signaling Pathway ◽

Luciferase Reporter Gene ◽

Migration Flow ◽

Gene Assay

Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids.

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miR-27b-3p Down-Regulation Prevents Hypoxia-Induced Cardiomyocyte Apoptosis Through Regulating Yes-Associated Protein 1 (YAP1) Expression

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2633 ◽

2021 ◽

Vol 11 (5) ◽

pp. 948-956

Author(s):

Lilin Wang ◽

Bo Feng ◽

Shu Zhu

Keyword(s):

Cell Viability ◽

Target Genes ◽

Luciferase Reporter ◽

Pcr Analysis ◽

H9c2 Cells ◽

Luciferase Reporter Gene ◽

Western Blot Assay ◽

Heart Protection ◽

Gene Assay ◽

Related Proteins

Background: Congenital heart disease (CHD) is one of the most common birth defects. MicroR-NAs (miRNAs) are a group of endogenous, non-coding small RNAs and mediate the target genes expression. An increasing evidence showed that in recent years, miRNAs have given rise to more and more attention in heart protection and development. In our research, the main purpose was to determine the effect of miR-27b-3p in CHD and analyze related mechanisms. Methods: We performed qRT-PCR analysis to examine miR-27b-3p expression in myocardial tissue from 30 patients with CHD and hypoxia-induced H9C2 cells. Then, we performed biological software TargetScan to predict the relationship of miR-27b-3p and YAP1, and dual luciferase reporter gene assay was used to verify the results. H9C2 cells were transfected with inhibitor control, miR-27b-3p inhibitor, miR-27b-3p inhibitor + control-siRNA or miR-27b-3p inhibitor + YAP1-siRNA for 6 hours and then induced by hypoxia for 72 hours. Subsequently, we performed MTT and FCM analysis to detect cell viability and apoptosis. Finally, we used western blot assay to measure the expression of apoptosis-related proteins. Results: Our study indicated that miR-27b-3p expression in myocardial samples of cyanotic CHD patients was significantly higher than that of the acyanotic CHD patients. miR-27b-3p expression was gradually up-regulated with the increase of hypoxia induction time in H9C2 cells. Besides, we confirmed that YAP1 was a target gene of miR-27b-3p. Moreover, our results showed that miR-27b-3p inhibitor improved cell viability, decreased apoptosis, and affected apoptosis-related proteins expression in hypoxia induced H9C2 cells. These changes were reversed by YAP1-siRNA. All data demonstrated that miR-27b-3p/YAP1 might be new potential bio-marker and therapeutic target for CHD treatment.

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miRNA-491-5p Inhibited Cell Proliferation in Human Hepatocellular Carcinoma Through Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2680 ◽

2021 ◽

Vol 11 (4) ◽

pp. 567-572

Author(s):

Weike Zhou ◽

Qian Zhu ◽

Jiang Shen

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Noncoding Rna ◽

Detection System ◽

Growth Factor Receptor ◽

Akt Signaling ◽

Luciferase Reporter ◽

Cell Multiplication ◽

Akt Signaling Pathway ◽

Luciferase Reporter Gene

miRNA-491-5p was a short, noncoding RNA, usually down-expressed in various human tumors and regulated biological functions. However, the connection between miRNA-491-5p and hepatocellular carcinoma (HCC) remained unclear. Therefore, the role of miRNA-491-5p played in HCC has been detected in this research. The results indicate that miRNA-491-5p is obviously diminished in tissues and cells of HCC (P < 0.001; P < 0.05). After miRNA-491-5p over-expressing, cell multiplication as well as invasion viability were significantly inhibited (P < 0.01). Double luciferase reporter gene detection system demonstrated epidermal growth factor receptor (EGFR) gene was considered directly target miR-491-5p, along with suppressed EGFR was observed in cells over-expressed miRNA-491-5p. Moreover, miRNA-491-5p functioned via the PI3K/Akt signaling pathway. Generally, this study illustrated that miRNA-491-5p promoted HCC progression via PI3K/Akt signaling pathway targeting EGFR, while miRNA-491-5p mimicking therapeutics may provide viable avenue for the medication of HCC.

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Mir10a overexpression aggravates the renal ischemia-reperfusion injury associated with a decrease in PIK3CA

10.21203/rs.2.23453/v2 ◽

2020 ◽

Author(s):

Dongsheng Xu ◽

Wenjun Li ◽

Tao Zhang ◽

Gang Wang

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Luciferase Reporter ◽

Akt Pathway ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

Underlying Mechanisms ◽

Related Proteins ◽

Hypoxia Reoxygenation

Abstract Background: To investigate the effect of miR-10a on the renal tissues with ischemia-reperfusion (I/R) injury in rats and explore the underlying mechanisms of miR-10a in the HK-2 cells of hypoxia-reoxygenation. Methods: The miR-10a level was measured in renal tissues with I/R rats by RT-PCR. In order to research the role of miR-10a in the renal tissues, miR-10 agonist and miR-10a antagonist were used to treat I/R rats. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in serum, renal histopathology, apoptosis of cells in renal tissues were analyzed, separately. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blot. The HK-2 cell was cultured to study the mechanism of miR-10a in the model of hypoxia-reoxygenation. The dual luciferase reporter gene assay was used to confirm the PI3K p100 catalytic subunit α (PIK3CA) was a target gene of miR-10a. Results: After renal I/R injury in rats, the miR-10a expression was significantly increased (p<0.05). Injection of miR-10a agonist significantly aggravated the injury of renal and raised the apoptosis of cells in renal in rats with renal I/R injury (p<0.05). However, administration of miR-10a antagonist obviously improved the injury of renal, decreased the renal cells apoptosis and inhibited the PI3K/Akt pathway activity (p<0.05). In vitro experiments, the negative relation between PIK3CA and miR-10a was confirmed. Further, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased the cells apoptosis via up-regulating PI3K/Akt pathway (p<0.05). Conclusion: miR-10a could aggravate the renal I/R injury associated with a decrease in PIK3CA/PI3K/Akt pathway.

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YY1 activates EMI2 and promotes the progression of cholangiocarcinoma through the PI3K/Akt signaling axis

Cancer Cell International ◽

10.1186/s12935-021-02328-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shuai Zhou ◽

Kang Lin Qu ◽

Jin Ang Li ◽

Shi Lei Chen ◽

Yi Gang Zhang ◽

...

Keyword(s):

Transcription Factors ◽

Bile Duct ◽

Signaling Pathway ◽

Akt Signaling ◽

Reporter Gene Assay ◽

Luciferase Reporter ◽

Akt Signaling Pathway ◽

Luciferase Reporter Gene ◽

Luciferase Reporter Gene Assay ◽

Gene Assay

Abstract Background Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. Methods The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. Results EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. Conclusion EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

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