scholarly journals MiR-34a Enhances Chondrocyte Apoptosis, Senescence and Facilitates Development of Osteoarthritis by Targeting DLL1 and Regulating PI3K/AKT Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 1304-1316 ◽  
Author(s):  
Wei Zhang ◽  
Peichun Hsu ◽  
Biao  Zhong ◽  
Shang Guo ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Target Genes ◽  
Cartilage Degeneration ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Chondrocyte Apoptosis ◽  
Articular Chondrocyte ◽  
Reporter System ◽  
Chondrocyte Death

Background/Aims: Osteoarthritis (OA) is the prevalent degenerative disease caused by various factors. MicroRNAs are important regulators in the inflammation and immune response. The aim of this study was to investigate the effect of microRNA-34a (MiR-34a) on the death of chondrocytes, senescence, as well as its role in OA progression. Methods: A series of experiments involving CCK-8, flow cytometry, β-galactosidase staining and wound healing assays were conducted to determine the cellular capabilities of proliferation, cell apoptosis, senescence and the ability of cells to recover from injury, respectively. Binding sites between miR-34a and delta-like protein 1 (DLL1) were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. OA model was generated via surgery. Results: We found that miR-34a expression was increased in the cartilage of OA patients. In rat chondrocytes and chondrosarcoma cells, miR-34a transfections noticeably inhibited the expression of DLL1, triggered cell death and senescence, suppressed proliferation, and prevented scratch assay wound closure. However, transfection of a miR-34a inhibitor displayed adverse effects. Additionally, secretion and expression of factors associated with cartilage degeneration were altered via miR-34a. Moreover, miR-34a directly inhibits DLL1 mRNA. Furthermore, concentrations of DLL1, total PI3K, and p-AKT declined in chondrocytes that overexpress miR-34a. DLL1 overexpression elevated PI3K and p-AKT levels, and eliminated cell death triggered by a miR-34a mimic. In vivo, miR-34a remarkably inhibited miR-34a up-regulation, while enhanced the level of DLL1 expression. In the knee joints of surgery-induced OA rats, articular chondrocyte death and loss of cartilage were attenuated via miR-34a antagomir injection. Conclusions: These findings indicate that miR-34a contributes to chondrocyte death, causing OA progression through DLL1 and modulation of the PI3K/AKT pathway.

scholarly journals miR-155 and miR-146a collectively regulate meningitic Escherichia coli infection-mediated neuroinflammatory responses

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Bo Yang ◽  
Ruicheng Yang ◽  
Bojie Xu ◽  
Jiyang Fu ◽  
Xinyi Qu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Target Genes ◽  
Microglia Activation ◽  
Luciferase Reporter ◽  
Reporter System ◽  
Negative Feedback Regulation ◽  
E Coli

Abstract Background Escherichia coli is the most common Gram-negative bacterium causing meningitis, and E. coli meningitis is associated with high mortality and morbidity throughout the world. Our previous study showed that E. coli can colonize the brain and cause neuroinflammation. Increasing evidence supports the involvement of miRNAs as key regulators of neuroinflammation. However, it is not clear whether these molecules participate in the regulation of meningitic E. coli-mediated neuroinflammation. Methods The levels of miR-155 and miR-146a, as well as their precursors, in E. coli-infected astrocytes were measured using quantitative real-time PCR (qPCR). Overexpression and knockdown studies of miR-155 and miR-146a were performed to observe the effects on bacterial loads, cytokines, chemokines, and NF-κB signaling pathways. Bioinformatics methods were utilized to predict the target genes, and these target genes were validated using qPCR, Western blotting, and luciferase reporter system. In vivo knockdown of miR-155 and miR-146a was carried out to observe the effects on bacterial loads, inflammatory genes, astrocyte activation, microglia activation, and survival in a mouse model. Results The levels of miR-155, miR-146a, and their precursors were significantly increased in astrocytes during E. coli infection. miR-155 and miR-146a were induced by the NF-κB-p65 signaling pathway upon infection. Overexpressing and inhibiting miR-155 and miR-146a in astrocytes did not affect the bacterial loads. Further, the in vitro overexpression of miR-155 and miR-146a suppressed the E. coli-induced inflammatory response, whereas the inhibition of miR-155 and miR-146a enhanced it. Mechanistically, miR-155 inhibited TAB2, and miR-146a targeted IRAK1 and TRAF6; therefore, they functioned collaboratively to modulate TLR-mediated NF-κB signaling. In addition, both miR-155 and miR-146a could regulate the EGFR–NF-κB signaling pathway. Finally, the in vivo suppression of E. coli-induced miR-155 and miR-146a further promoted the production of inflammatory cytokines, aggravated astrocyte and microglia activation, and decreased mouse survival time, without affecting the bacterial loads in the blood and brain. Conclusions E. coli infection induced miR-155 and miR-146a, which collectively regulated bacteria-triggered neuroinflammatory responses through negative feedback regulation involving the TLR-mediated NF-κB and EGFR–NF-κB signaling pathways, thus protecting the central nervous system from further neuroinflammatory damage.

scholarly journals miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽  
2021 ◽  
pp. 194760352110235
Author(s):  
Hongjun Zhang ◽  
Wendi Zheng ◽  
Du Li ◽  
Jia Zheng
Keyword(s):  
Caspase 3 ◽  
Cartilage Tissue ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Knee Cartilage ◽  
Before And After ◽  
Related Proteins ◽  
Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

scholarly journals Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Junjie Cen ◽  
Yanping Liang ◽  
Yong Huang ◽  
Yihui Pan ◽  
Guannan Shu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Target Genes ◽  
Expression Patterns ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

scholarly journals CircWAC induces chemotherapeutic resistance in triple-negative breast cancer by targeting miR-142, upregulating WWP1 and activating the PI3K/AKT pathway

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lei Wang ◽  
Yehui Zhou ◽  
Liang Jiang ◽  
Linlin Lu ◽  
Tiantian Dai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Chemotherapeutic Resistance ◽  
Repressive Effect

Abstract Background Chemotherapeutic resistance is the main cause of clinical treatment failure and poor prognosis in triple-negative breast cancer (TNBC). There is no research on chemotherapeutic resistance in TNBC from the perspective of circular RNAs (circRNAs). Methods TNBC-related circRNAs were identified based on the GSE101124 dataset. Quantitative reverse transcription PCR was used to detect the expression level of circWAC in TNBC cells and tissues. Then, in vitro and in vivo functional experiments were performed to evaluate the effects of circWAC in TNBC. Results CircWAC was highly expressed in TNBC and was associated with worse TNBC patient prognosis. Subsequently, it was verified that downregulation of circWAC can increase the sensitivity of TNBC cells to paclitaxel (PTX) in vitro and in vivo. The expression of miR-142 was negatively correlated with circWAC in TNBC. The interaction between circWAC and miR-142 in TNBC cells was confirmed by RNA immunoprecipitation assays, luciferase reporter assays, pulldown assays, and fluorescence in situ hybridization. Mechanistically, circWAC acted as a miR-142 sponge to relieve the repressive effect of miR-142 on its target WWP1. In addition, the overall survival of TNBC patients with high expression of miR-142 was significantly better than that of patients with low expression of miR-142, and these results were verified in public databases. MiR-142 regulated the expression of WWP1 and the activity of the PI3K/AKT pathway. It was confirmed that WWP1 is highly expressed in TNBC and that the prognosis of patients with high WWP1 expression is poor. Conclusions CircWAC/miR-142/WWP1 form a competing endogenous RNA (ceRNA) network to regulate PI3K/AKT signaling activity in TNBC cells and affect the chemosensitivity of cells.

scholarly journals miR-182-5p and miR-378a-3p regulate ferroptosis in I/R-induced renal injury

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Chenguang Ding ◽  
Xiaoming Ding ◽  
Jin Zheng ◽  
Bo Wang ◽  
Yang Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Renal Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Renal Tubular Cell ◽  
In Cells

Abstract Renal tubular cell death is the key factor of the pathogenesis of ischemia/reperfusion (I/R) kidney injury. Ferroptosis is a type of regulated cell death (RCD) found in various diseases. However, the underlying molecular mechanisms related to ferroptosis in renal I/R injury remain unclear. In the present study, we investigated the regulatory role of microRNAs on ferroptosis in I/R-induced renal injury. We established the I/R-induced renal injury model in rats, and H/R induced HK-2 cells injury in vitro. CCK-8 was used to measure cell viability. Fe2+ and ROS levels were assayed to evaluate the activation of ferroptosis. We performed RNA sequencing to profile the miRNAs expression in H/R-induced injury and ferroptosis. Western blot analysis was used to detect the protein expression. qRT-PCR was used to detect the mRNA and miRNA levels in cells and tissues. We further used luciferase reporter assay to verify the direct targeting effect of miRNA. We found that ischemia/reperfusion-induced ferroptosis in rat’s kidney. We identified that miR-182-5p and miR-378a-3p were upregulated in the ferroptosis and H/R-induced injury, and correlates reversely with glutathione peroxidases 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression in renal I/R injury tissues, respectively. In vitro studies showed that miR-182-5p and miR-378a-3p induced ferroptosis in cells. We further found that miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3′UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced renal injury in rats. In conclusion, we demonstrated that I/R induced upregulation of miR-182-5p and miR-378a-3p, leading to activation of ferroptosis in renal injury through downregulation of GPX4 and SLC7A11.

scholarly journals CircRNA PIP5K1A promotes the progression of glioma through upregulation of TCF12/PI3K/AKT pathway by sponging miR-515-5p

2020 ◽  
Author(s):  
Kebin Zheng ◽  
Haipeng Xie ◽  
Xiaosong Wu ◽  
Xichao Wen ◽  
Zhaomu Zeng ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Normal Tissues

Abstract BackgroundIncreasing studies have revealed that circular RNAs (CircRNAs) make great contribution to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A in glioma. MethodsFirstly, RT-PCR was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and a cell model of CircPIP5K1A overexpression and knockdown was constructed. Subsequently, cell proliferation and viability were detected by CCK8 method and BrdU staining, apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (including Caspase3, Bax and Bcl2) and epithelial-mesenchymal transition (EMT) markers (including E-cadherin, Vimentin and N-cadherin) by western blot or RT-PCR. ResultsThe results manifested that CircPIP5K1A was obviously upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was distinctly related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated the proliferation, invasion, EMT of glioma cells, and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A also upregulated TCF12 and PI3K/AKT pathway activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while dual luciferase reporter assay and RNA immunocoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3'-untranslated region (UTR) of TCF12. ConclusionsAltogether, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates the development of glioma through the modulating miR-515-5p mediated TCF12/PI3K/AKT axis.

scholarly journals The Role of BCL6 in Glioblastoma

2021 ◽  
Author(s):  
◽  
Nicole Jones
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Target Genes ◽  
Therapy Resistance ◽  
Response To Therapy ◽  
Transcriptional Analysis ◽  
Luciferase Reporter ◽  
Mobility Shift ◽  
Response To Chemotherapy ◽  
Targeted Inhibition

<p>Glioblastoma (GBM) is the most common and most deadly brain tumour to occur in adults. Initially patients respond to radiation and chemotherapy, which primarily work by causing large amounts of DNA damage, leading to cell death. However, this process does not happen effectively in GBM and understanding how these cells resist cell death in response to therapy is key to improving the efficacy of treatment. BCL6 is a transcription factor that stops cell death in response to DNA damage, primarily through repressing transcription of DNA damage response genes. Recent work in our lab has shown BCL6 to be present in untreated GBM tumours and up-regulated in GBM cells treated with chemotherapy or radiation, and inhibition of BCL6 leads to a profound loss in proliferative activity. These results indicate that BCL6 may be used as a mechanism of therapy resistance in GBM cells. The objective of this study was to establish a role for BCL6 in GBM cells using luciferase reporter assays, electrophoretic mobility shift assays (EMSA), quantitative chromatin immunoprecipitation (qChIP) and targeted inhibition of BCL6 with subsequent transcriptional analysis by RNA sequencing. We observed that BCL6 appeared to be a transcriptional activator in GBM, as shown by increased luciferase activity in GBM cells treated with radiation. EMSA experiments revealed that overexpressed BCL6 formed complexes with co-repressors, but endogenous BCL6 did not. qChIP experiments revealed that BCL6 was not bound to tradtional BCL6 target genes. Analysis of transcriptional profiles has identified a unique subset of genes which are downregulated when BCL6 is inhibited and upregulated in response to chemotherapy, and these genes were related to cell survival. These changes indicate that these genes may be regulated by BCL6 in chemotherapy treated cells. Together, these results illustrate that BCL6 appears to have an active and unique function in GBM cells, and reinforces this transcription factors position as an attractive therapeutic target in GBM.</p>

MiR-30a-5p Downregulation Induces Neuronal Autophagy by Activating AMPK After 2856MHz Microwave Radiation

2021 ◽  
Author(s):  
Yanhui Hao ◽  
Wenchao Li ◽  
Hui Wang ◽  
Jing Zhang ◽  
Haoyu Wang ◽  
...  
Keyword(s):  
Microwave Radiation ◽  
Hippocampal Neurons ◽  
Target Genes ◽  
Neuronal Damage ◽  
Luciferase Reporter ◽  
Potential Health ◽  
Downstream Target ◽  
Neuronal Autophagy

Abstract Background With the development of science and technology, microwaves are being widely used. More and more attention has been paid to the potential health hazards of microwave exposure. The regulation of miR-30a-5p (miR-30a) on autophagy is involved in the pathophysiological process of many diseases. Our previous study found that 30 mW/cm2 microwave radiation could reduce miR-30a expression and activate neuronal autophagy in rat hippocampus. However, the roles played by miR-30a in microwave-induced neuronal autophagy and related mechanisms remain largely unexplored. Results In the present study, we established neuronal damage models by exposing rat hippocampal neurons and rat adrenal pheochromocytoma (PC12) cell-derived neuron-like cells to 30 mW/cm2 microwave, which resulted in miR-30a downregulation and autophagy activation in vivo and in vitro. Bioinformatics analysis was conducted, and Beclin1, Prkaa2, Irs1, Pik3r2, Rras2, Ddit4, Gabarapl2 and autophagy-related gene 12 (Atg12) were identified as potential downstream target genes of miR-30a involved in regulating autophagy. Based on our previous findings that microwave radiation can cause a neuronal energy metabolism disorder, Prkaa2, encoding adenosine 5’-monophosphate-activated protein kinase α2 (AMPKα2, an important catalytic subunit of energy sensor AMPK), was selected for further analysis. Dual-luciferase reporter assay results showed that Prkaa2 is a downstream target gene of miR-30a. Microwave radiation increased the expression and phosphorylation (Thr172) of AMPKα both in vivo and in vitro. Moreover, the transduction of cells with miR-30a mimics suppressed AMPKα2 expression, inhibited AMPKα (Thr172) phosphorylation and reduced autophagy flux in neuron-like cells. Importantly, miR-30a mimics abolished microwave-activated autophagy and inhibited microwave-induced AMPKα (Thr172) phosphorylation. Conclusions AMPKα2 was a newly founded downstream gene of miR-30a involved in autophagy regulation, and miR-30a downregulation after microwave radiation could promote neuronal autophagy by increasing AMPKα2 expression and activating AMPK signaling.

scholarly journals Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Guiqiang Miao ◽  
Xuehui Zang ◽  
Huige Hou ◽  
Hui Sun ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Cartilage Degeneration ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Reporter Assay ◽  
Proapoptotic Protein ◽  
Regulation Mechanisms ◽  
Direct Target

Osteoarthritis (OA) is a chronic degenerative joint disease, where chondrocyte apoptosis is responsible for cartilage degeneration. Bax is a well-known proapoptotic protein of the Bcl-2 family, involved in a large number of physiological and pathological processes. However, the regulation mechanisms of Bax underlying chondrocyte apoptosis in OA remain unknown. In the present study, we determined the role of Bax in human OA and chondrocyte apoptosis. The results showed that Bax was upregulated in chondrocytes from the articular cartilage of OA patients and in cultured chondrocyte-like ATDC5 cells treated by IL-1β. Bax was identified to be the direct target of miR-29a by luciferase reporter assay and by western blotting. Inhibition of miR-29a by the mimics protested and overexpression by miR-29a inhibitors aggravated ATDC5 apoptosis induced by IL-1β. These data reveal that miR-29a/Bax axis plays an important role in regulating chondrocyte apoptosis and suggest that targeting the proapoptotic protein Bax and increasing expression levels of miR-29a emerge as potential approach for protection against the development of OA.

scholarly journals MACC1 Suppresses Cell Apoptosis in Hepatocellular Carcinoma by Targeting the HGF/c-MET/AKT Pathway

2015 ◽  
Vol 35 (3) ◽  
pp. 983-996 ◽  
Author(s):  
Yingmin Yao ◽  
Chanwei Dou ◽  
Zhongtang Lu ◽  
Xin Zheng ◽  
Qingguang Liu
Keyword(s):  
Cell Apoptosis ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Annexin V ◽  
Akt Pathway ◽  
Caspase 9 ◽  
Dapi Staining ◽  
In Vivo Experiments

Background & Aims: To investigate the expression and prognostic value of MACC1 in patients with HCC and identify the mechanism by which MACC1 inhibits HCC cell apoptosis. Methods: MACC1 and p-AKT expression was studied using immunohistochemistry of both HCC tissues and adjacent liver tissues. qRT-PCR and western immunoblotting were used to examine the expression of target genes at the mRNA and protein levels, respectively. The MTT assay was used to assess cell viability, and cell apoptosis was determined by DAPI staining, Annexin V/PI staining and Caspase 3/7 assay. Nude mice were used to perform in vivo experiments. Results: The overexpression of MACC1 was found in HCC tissues and was correlated with poor postsurgical prognosis. There was a positive relationship between MACC1 and p-AKT expression in HCC tissues. In vitro experiments showed that MACC1 repressed HCC cell apoptosis and promoted cell growth. Knockdown of c-MET abolished the anti-apoptotic function of MACC1. Next, MACC1 was verified to activate PI3K/AKT signaling by sensitizing HGF/c-MET signaling in HCC. MACC1 overexpression enhanced the HGF-driven phosphorylation of BAD, Caspase 9 and FKHRL1 and inhibited their pro-apoptotic functions in HCC cells. Finally, MACC1 was shown to inhibit cell apoptosis and promote HCC growth in vivo. Conclusions: This investigation revealed that MACC1 overexpression predicted worse prognosis after liver resection, which was attributed to the repression of HCC cell apoptosis via a molecular mechanism in which MACC1 accelerated the activation of the HGF/c-MET/PI3K/AKT pathway and phosphorylated BAD, Caspase 9 and FKHRL1, ultimately preventing their nuclear translocation and their pro-apoptotic function.

Sign in / Sign up

Export Citation Format

Share Document