MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4

2021 ◽  
pp. 153537022110230
Author(s):  
Zhichang Pan ◽  
Yu Zhang ◽  
Chuanyong Li ◽  
Yuan Yin ◽  
Rui Liu ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Vascular Function ◽  
Critical Role ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Related Factor ◽  
Related Factors ◽  
Mesenchymal Transition ◽  
S100a4 Expression

Deep venous thrombosis is one of the most common venous thromboembolic diseases and has a low cure rate and a high postoperative recurrence rate. Furthermore, emerging evidence indicates that microRNAs are involved in deep venous thrombosis. miR-296-5p is an important microRNA that plays a critical role in various cellular functions, and S100A4 is closely related to vascular function. miR-296-5p is downregulated in deep venous thrombosis patients, and its predicted target S100A4 is upregulated in deep venous thrombosis patients. Therefore, it was hypothesized that miR-296-5p may play a vital role in the development of deep venous thrombosis by targeting S100A4. An Ox-LDL-stimulated HUVEC and deep venous thrombosis mouse model was employed to detect the biological functions of miR-296-5p and S100A4. Dual luciferase reporter assays and pull-down assays were used to authenticate the interaction between miR-296-5p and S100A4. ELISA and Western blotting were employed to detect the protein levels of thrombosis-related factors and the endothelial-to-mesenchymal transition (EndMT)-related factors. The miR-296-5p levels were reduced, while the S100A4 levels were enhanced in deep venous thrombosis patients, and the miR-296-5p levels were negatively correlated with the S100A4 levels in deep venous thrombosis patients. miR-296-5p suppressed S100A4 expression by targeting the 3ʹ UTR of S100A4. MiR-296-5p knockdown accelerated ox-LDL-induced HUVEC apoptosis, oxidative stress, thrombosis-related factor expression, and EndMT, while S100A4 knockdown antagonized these effects in ox-LDL-induced HUVECs. S100A4 knockdown reversed the effect induced by miR-296-5p knockdown. Moreover, the in vivo studies revealed that miR-296-5p knockdown in deep venous thrombosis mice exacerbated deep venous thrombosis formation, whereas S100A4 knockdown had the opposite effect. These results indicate that elevated miR-296-5p inhibits deep venous thrombosis formation by inhibiting S100A4 expression. Both miR-296-5p and S100A4 may be potential diagnostic markers and therapeutic targets for deep venous thrombosis.

scholarly journals Incidence and risk factors for deep venous thrombosis of lower extremity after surgical treatment of isolated patella fractures

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhanchao Tan ◽  
Hongzhi Hu ◽  
Xiangtian Deng ◽  
Jian Zhu ◽  
Yanbin Zhu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lower Extremity ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Medical Data ◽  
Limited Information ◽  
Related Factors ◽  
Patella Fractures ◽  
Independent Risk Factors ◽  
Associated Risk Factors

Abstract Background Limited information exists on the incidence of postoperative deep venous thromboembolism (DVT) in patients with isolated patella fractures. The objective of this study was to investigate the postoperative incidence and locations of deep venous thrombosis (DVT) of the lower extremity in patients who underwent isolated patella fractures and identify the associated risk factors. Methods Medical data of 716 hospitalized patients was collected. The patients had acute isolated patella fractures and were admitted at the 3rd Hospital of Hebei Medical University between January 1, 2016, and February 31, 2019. All patients met the inclusion criteria. Medical data was collected using the inpatient record system, which included the patient demographics, patient’s bad hobbies, comorbidities, past medical history, fracture and surgery-related factors, hematological biomarkers, total hospital stay, and preoperative stay. Doppler examination was conducted for the diagnosis of DVT. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors. Results Among the 716 patients, DVT was confirmed in 29 cases, indicating an incidence of 4.1%. DVT involved bilateral limbs (injured and uninjured) in one patient (3.4%). DVT involved superficial femoral common vein in 1 case (3.4%), popliteal vein in 6 cases (20.7%), posterior tibial vein in 11 cases (37.9%), and peroneal vein in 11 cases (37.9%). The median of the interval between surgery and diagnosis of DVT was 4.0 days (range, 1.0-8.0 days). Six variables were identified to be independent risk factors for DVT which included age category (> 65 years old), OR, 4.44 (1.34-14.71); arrhythmia, OR, 4.41 (1.20-16.15); intra-operative blood loss, OR, 1.01 (1.00-1.02); preoperative stay (delay of each day), OR, 1.43 (1.15-1.78); surgical duration, OR, 1.04 (1.03-1.06); LDL-C (> 3.37 mmol/L), OR, 2.98 (1.14-7.76). Conclusion Incidence of postoperative DVT in patients with isolated patella fractures is substantial. More attentions should be paid on postoperative DVT prophylaxis in patients with isolated patella fractures. Identification of associated risk factors can help clinicians recognize the risk population, assess the risk of DVT, and develop personalized prophylaxis strategies.

scholarly journals MicroRNA-29a Suppresses CD36 to Ameliorate High Fat Diet-Induced Steatohepatitis and Liver Fibrosis in Mice

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1298 ◽  
Author(s):  
Hung-Yu Lin ◽  
Feng-Sheng Wang ◽  
Ya-Ling Yang ◽  
Ying-Hsien Huang
Keyword(s):  
Transcription Factor ◽  
Liver Fibrosis ◽  
High Fat Diet ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Hepatic Tissue ◽  
Wild Type ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Mesenchymal Transition

MicroRNA-29 (miR-29) has been shown to play a critical role in reducing inflammation and fibrosis following liver injury. Non-alcoholic fatty liver disease (NAFLD) occurs when fat is deposited (steatosis) in the liver due to causes other than excessive alcohol use and is associated with liver fibrosis. In this study, we asked whether miR-29a could reduce experimental high fat diet (HFD)-induced obesity and liver fibrosis in mice. We performed systematical expression analyses of miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates subjected to HFD-induced NAFLD. The results demonstrated that increased miR-29a not only alleviated HFD-induced body weight gain but also subcutaneous, visceral, and intestinal fat accumulation and hepatocellular steatosis in mice. Furthermore, hepatic tissue in the miR-29aTg mice displayed a weak fibrotic matrix concomitant with low fibrotic collagen1α1 expression within the affected tissues compared to the wild-type (WT) mice fed the HFD diet. Increased miR-29a signaling also resulted in the downregulation of expression of the epithelial mesenchymal transition-executing transcription factor snail, mesenchymal markers vimentin, and such pro-inflammation markers as il6 and mcp1 within the liver tissue. Meanwhile, miR-29aTg-HFD mice exhibited significantly lower levels of peroxisome proliferator-activated receptor γ (PPARγ), mitochondrial transcription factor A TFAM, and mitochondria DNA content in the liver than the WT-HFD mice. An in vitro luciferase reporter assay further confirmed that miR-29a mimic transfection reduced fatty acid translocase CD36 expression in HepG2 cells. Conclusion: Our data provide new insights that miR-29a can improve HDF-induced obesity, hepatocellular steatosis, and fibrosis, as well as highlight the role of miR-29a in regulation of NAFLD.

A Novel TWIST2-ID2 Axis That Modulates The Growth and Imatinib Sensitivity Of CML CD34+ Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 511-511
Author(s):  
Yun Zhao ◽  
Wenjuan Ma ◽  
Xiuyan Zhang ◽  
Jiangxia Cui ◽  
Ivan Sloma ◽  
...  
Keyword(s):  
Dna Binding ◽  
Progenitor Cells ◽  
Lentiviral Vector ◽  
Critical Role ◽  
K562 Cells ◽  
Luciferase Reporter ◽  
Control Group ◽  
Wild Type ◽  
Mesenchymal Transition ◽  
Cd34 Cells

Abstract TWIST is a basic helix-loop-helix transcription factor that specifies Drosophila mesoderm development. In mammals there are 2 members, TWIST1 and TWIST2. TWIST2 is a regulator of osteoblasts and muscle development and plays a critical role in the epithelial-mesenchymal transition process, as well as in cancer initiation and metastasis. Twist2-deficient mice develop a myeloproliferative disease. These findings led us to query a potential role of TWIST2 in normal and leukemic (CML) human hematopoietic cells. RT-PCR and immuno-fluorescence analysis of CD34+ bone marrow (BM) cells obtained from healthy donors demonstrated their expression of TWIST2 transcripts and protein. Lentiviral vector-mediated knockdown of TWIST2 with 2 independent shRNA sequences enhanced the erythroid and granulopoietic colony-forming activity of transduced normal BM cells ∼2-fold compared with control transduced cells (n=3, p<0.05). Interestingly, ChIP studies showed that TWIST2 can bind directly to the DNA promoter for ID2 in CD34-enriched BM cells and knockdown of TWIST2 reduced ID2 expression by 50%. In lin-CD34+ cells from 14 chronic myeloid leukemia (CML) patients, we found both TWIST2 and ID2 transcripts to be 5 and 6 fold lower than those from 6 healthy BM donors (p<0.05), with similar findings for TWIST2 and ID2 protein in the same cells. BCR-ABL1-transduced Baf/3 cells also showed a reduction in Twist2 expression. Conversely, TWIST2 expression became elevated when K562 cells were treated with Imatinib mesylate (IM). We then generated a lentiviral vector encoding TWIST2 which proved capable of inhibiting the growth of K562 and MEG-01 cells as well as CFC production from CML CD34+ cells (n=11, p<0.05). Overexpression of TWIST2 in MEG-01 cells also reduced their tumorigenic ability in subcutaneously injected nude mice (0/8 for TWIST2 group, 7/8 for control group). In addition, increased TWIST2 sensitized the IM response of K562 cells and IM-resistant CD34+ cells from CML patients (2 in chronic phase and 2 in blast crisis). Correspondingly, knockdown of TWIST2 in K562 cells enhanced their cloning efficiency by 15% and made them IM-resistant. To obtain further insight into these biological effects of TWIST2, we generated several TWIST2 mutant cDNAs, including ones with a N-terminal truncation (ΔN), a C-terminal truncation (ΔC), a F86P dimerization mutant and a b- DNA binding mutant. Analysis of the effects of these mutants when overexpressed in CML cells and cell lines showed TWIST2 dimer formation was critical for the effects obtained with wild-type TWIST2, whereas the DNA binding domain could modulate these effects but was not essential, and the N-terminal and C-terminal domains were dispensable. We also found that overexpression of TWIST2 enhanced ID2 expression in CML CD34+ cells (n=3), as well as K562 and MEG-01 cells, and ChIP analyses confirmed the binding of TWIST2 to ID2 promoter DNA from K562 and MEG-01 cells. Using ID2 promoter-driven luciferase reporter and a mutant derivative (with only the E-box sequence altered), we found that TWIST2 could activate the wild-type promoter but not the mutated one in both K562 and MEG-01 cells. Finally, we co-transduced CML cells from 3 patients with TWIST2 and shRNA against ID2 and found that this reversed the suppressed production of CFC obtained with TWIST2 alone. Similarly in K562 cells this treatment partially restored their growth rate and IM resistance. Taken together, we report a novel TWIST2-ID2 regulatory axis in normal hematopoietic progenitor cells, which can also modulate the growth and IM response of CML progenitor cells. These findings provide a baseline for the future development of more effective therapy of CML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals LncRNA SNHG6 knockdown inhibits cisplatin resistance and progression of gastric cancer through miR-1297/BCL-2 axis

2021 ◽  
Author(s):  
Jiazhuan Mei ◽  
Guiju Liu ◽  
Ruijun Li ◽  
Peng Xiao ◽  
Dan Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cisplatin Resistance ◽  
B Cell Lymphoma ◽  
Luciferase Reporter ◽  
Related Factors ◽  
Mesenchymal Transition ◽  
Inhibition Concentration ◽  
Keywords Gastric Cancer ◽  
Resistant Cells

Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelia-mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were upregulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment. &#160;Keywords: Gastric cancer, cisplatin resistance, lncRNA SNHG6, miR-1297, BCL-2

scholarly journals Cholangiocyte-Derived Exosomal Long Noncoding RNA PICALM-AU1 Promotes Pulmonary Endothelial Cell EndMT in Hepatopulmonary Syndrome

2021 ◽  
Author(s):  
Congwen Yang ◽  
Yihui Yang ◽  
Yang Chen ◽  
Jian Huang ◽  
Caiyi Li ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Critical Role ◽  
Cell Communication ◽  
Hepatopulmonary Syndrome ◽  
Clinical Problem ◽  
Luciferase Reporter ◽  
Target Cells ◽  
Common Bile Duct Ligation ◽  
Mesenchymal Transition ◽  
Duct Ligation

Abstract Background: Hepatopulmonary syndrome (HPS) is an important clinical problem with limited understanding of disease pathologies. Exosome mediated cell-cell communication can modulate various cellular functions by transferring a variety of intracellular components to target cells. A new lncRNA PICALM-AU1 was found and upregulated in the liver of subjects with HPS. However, the expression and biological functions of the lncRNA PICALM-AU1 are still unknown. Methods: HPS rat model was constructed by common bile duct ligation (CBDL). RNA macroarray was used to analyze the expression differential lncRNAs in HPS rat liver. PICALM-AU1 expression in the serum exosome was measured in 56 HPS patients and in 73 patients with liver cirrhosis but not HPS. qPCR, Fluorescence in situ hybridization were used to analyze PICALM-AU1 expression and location. Virus derived PICALM-AU1 upregulation and down regulation were applied in rats and PMVECs cells. The effects of PICALM-AU1 on PMVECs was determined via CCK8 assay and transwell assay. PICALM-AU1 and miR144-3p relationship was analysis by Dual-luciferase reporter assay.Results: In this study, we found lncRNA PICALM-AU1 expressed in the cholangiocyte of liver, secreted as exosome into the serum. PICALM-AU1 carrying serum exosomes induced endothelial-mesenchymal transition (EndMT) of PMVECs and promoted lung injury. Furthermore, overexpression of PICALM-AU1 significantly suppressed miR144-3p and subsequently induced ZEB1 expression.Conclusions: Taken together, our findings present a road map of targeting the newly identified cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the pathologic angiogenesis of HPS by promoting EndMT and represents a potential therapeutic target for HPS.

scholarly journals UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Yan Wu ◽  
Dan Jin ◽  
Xiaohong Wang ◽  
Jing Du ◽  
Weihua Di ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Resistant Cell ◽  
Immunofluorescent Staining ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Novel Therapy ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Resistant Cells

Objectives. Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance.Methods. The mRNA expression ofUBE2C,ZEB1/2,ABCG2, andERCC1was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining. Cell proliferation was detected by CCK8 and MTT assays. Cell migration and invasion were analyzed by wound healing assay and Transwell assays. Promoter activities and gene transcription were analyzed by luciferase reporter assay.Results.In this study, we examined the effect of UBE2C and ZEB1/2 expression levels in DDP-resistant cells of NSCLC. We confirmed that aberrant expression of UBE2C and ZEB1/2 plays a critical role in repressing the DDP sensitivity to NSCLC cells. Additionally, knockdown of UBE2C significantly sensitized resistant cells to DDP by repressing the expression of ZEB1/2. Mechanistic investigations indicated that UBE2C transcriptionally regulated ZEB1/2 by accelerating promoter activity. This study revealed that ZEB1/2 promotes the epithelial mesenchymal transition and expression of ABCG2 and ERCC1 to participate in UBE2C-mediated NSCLC DDP-resistant cell progression, metastasis, and invasion.Conclusion. UBE2C may be a novel therapy target for NSCLC for sensitizing cells to the chemotherapeutic agent DDP.

scholarly journals MicroRNA-625 inhibits cell invasion and epithelial–mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yuan Li ◽  
Chenjuan Tao ◽  
Lili Dai ◽  
Caixia Cui ◽  
Chaohui Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Expression Levels

AbstractIntroduction: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC.Materials and methods: LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3′-UTR of SOX4.Results: The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells.Conclusions: Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease.

scholarly journals EGF-Mediated Overexpression of Myc Attenuates miR-26b by Recruiting HDAC3 to Induce Epithelial-Mesenchymal Transition of Lens Epithelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ning Dong ◽  
Bing Xu ◽  
Jingmei Xu
Keyword(s):  
Epithelial Cells ◽  
Egf Receptor ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Egfr Signaling ◽  
Mesenchymal Transition ◽  
And Migration

The previous study has demonstrated that epidermal growth factor (EGF) and EGF receptor (EGFR) signaling plays a critical role in the development of posterior capsule opacification (PCO) through regulating lens epithelial cells (LECs) proliferation. Recent studies have suggested that the residual LECs undergo proliferation and migration, and epithelial-mesenchymal transition (EMT) is the important cause of PCO formation after cataract surgery. EMT of LECs is considered to be playing a central role in the pathogenesis of PCO. In the present study, we investigated whether and how EGF may regulate EMT of LECs. First, we demonstrated that EGF and EGFR signaling induces Myc overexpression in primary human lens epithelial cells (HLECs). In turn, Myc overexpression could inhibit miR-26b by recruitment of HDAC3. Consequently, the downregulated expression of miR-26b increased the expression of EZH2 in primary HLECs. Mechanistically, miR-26b directly controls EZH2 expression by targeting its 3′-UTR in HLECs by luciferase reporter assays. Finally, we demonstrated that EGF induces the expression of EMT markers in primary HLECs via a miR-26b-dependent mechanism. In summary, EGF activated Myc and Myc overexpression inhibited miR-26b by recruitment of HDAC3, which in turn induced the expression of EZH2 and promoted the progression of EMT in HLECs.

scholarly journals Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guili Xu ◽  
Peng Zhang ◽  
Hansi Liang ◽  
Yunhua Xu ◽  
Jian Shen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
And Function

Abstract Background Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness. Methods Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells. Results miR-145 directly targeted the PD-L1 3′-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues. Conclusion Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.

scholarly journals CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 104-116
Author(s):  
Xiaobo Chen ◽  
Hongwen Sun ◽  
Yunping Zhao ◽  
Jing Zhang ◽  
Guosheng Xiong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Ec Cells

AbstractBackgroundThe aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC.MethodsThe protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay.ResultsWe discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities.ConclusionCirc_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

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