microR-505/heterogeneous nuclear ribonucleoprotein M inhibits hepatocellular carcinoma cell proliferation and induces cell apoptosis through the Wnt/β-catenin signaling pathway

2020 ◽  
Vol 14 (11) ◽  
pp. 981-996
Author(s):  
Xiaobin Chi ◽  
Yi Jiang ◽  
Yongbiao Chen ◽  
Lizhi Lv ◽  
Jianwei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Apoptosis Assay ◽  
Proliferation And Metastasis ◽  
Novel Strategy ◽  
Nuclear Ribonucleoprotein

Aim: This study aimed to investigate the expression of microRNA-505 (miR-505) and explore its clinical significance, biological function and mechanisms in hepatocellular carcinoma (HCC). Methods: Expression of miR-505 was measured in 128 paired HCC tissues and five cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay, Transwell migration, invasion assays and apoptosis assay were performed to explore the functional role of miR-505. The target gene of miR-505 was assessed using the bioinformatics assay and the related signaling pathway was confirmed using western blot. Results: Expression of miR-505 in HCC serum and tissues were downregulated. The overexpression of miR-505 in HCC cells inhibited cell proliferation and metastasis, as well as enhanced cell apoptosis by directly downregulating heterogeneous nuclear ribonucleoprotein M ( HNRNPM). The activity of the Wnt/β-catenin signaling pathway was suppressed by the overexpression of miR-505 but was promoted by the upregulation of HNRNPM. Conclusion: The results suggest that the regulation of miR-505/ HNRNPM may be a novel strategy to improve the targeted therapy of HCC.

scholarly journals Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion via Ras/MAPK Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiejun Hu ◽  
Dong Cai ◽  
Zhibo Zhao ◽  
Guo-Chao Zhong ◽  
Jianping Gong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Advanced Tumor Stage ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Tumor Tissues ◽  
Nuclear Ribonucleoprotein

Hepatocellular carcinoma (HCC), the most common malignant tumor, has high fatality and recurrence rates. Accumulating evidence shows that heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is mainly involved in RNA splicing, export, and translation, promotes progression and metastasis of multiple tumor types; however, the effects of HNRNPC in HCC are unknown. In the present study, high levels of HNRNPC were detected in tumor tissues compared with para-tumor tissues by immunohistochemical and western blot assays. Furthermore, Cox proportional hazards regression models, the Kaplan–Meier method, and clinicopathologic features analysis showed that HNRNPC was not only an independent prognostic factor for both overall and disease-free survival in HCC but also a predictor of large tumor size and advanced tumor stage. Functional experiments revealed that silencing of HNRNPC not only led to arrest of more HCC cells at G0/G1 phase to inhibit their proliferation, but also suppressed EMT process to block their invasion, and migration in vitro; this was related to the Ras/MAPK signaling pathway. In addition, blocking of HCC cell proliferation regulated by HNRNPC silencing was observed in vivo. Finally, rescue tests showed that after recovery of Ras/MAPK signaling pathway activity by treatment with Ras agonists, the proliferation, migration, and invasion suppression of Huh-7 and Hep 3B cell lines caused by HNRNPC knockdown was partially reversed. Taken together, these results indicate that HNRNPC knockdown inhibits HCC cell proliferation, migration and invasion, in part via the Ras/MAPK signaling pathway. Thus, HNRNPC may have an important role in the progression of HCC and represents a promising biomarker for evaluation of prognosis and a potential therapeutic target in HCC patients.

scholarly journals Overexpression of long non-coding RNA LINC00982 suppresses cell proliferation and tumor growth of papillary thyroid carcinoma through PI3K-ATK signaling pathway

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Debin Xu ◽  
Jichun Yu ◽  
Shimin Zhuang ◽  
Shuyong Zhang ◽  
Zhengdong Hong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
And Migration ◽  
Proliferation And Migration

Abstract Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan–Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo. Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo. Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.

Long non-coding RNA ZEB1-AS1 promotes proliferation and metastasis of hepatocellular carcinoma cells by targeting miR-299-3p/E2F1 axis

2021 ◽  
Author(s):  
Baiyin Mu ◽  
Chenlan Lv ◽  
Qingli Liu ◽  
Hong Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Tumorigenesis And Progression ◽  
Novel Biomarkers ◽  
Proliferation And Metastasis ◽  
Long Non Coding Rna

Abstract There is emerging evidence that dysregulation of long non-coding RNAs (lncRNAs) is associated with hepatocellular carcinoma (HCC). Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) functions as an oncogenic regulator in various malignancies. Nonetheless, the potential role of ZEB1-AS1 in HCC remains poorly elucidated. Herein, qRT-PCR was employed for examining ZEB1-AS1, miR-299-3p and E2F1 mRNA expressions in HCC cells and tissues. MTT assay was performed to evaluate cell proliferation. Transwell assay was utilized for evaluating cancer cell migration and invasion. Western blot was employed for measuring E2F1 protein expression. What’s more, dual-luciferase reporter assay was utilized for verifying the targeting relationships between ZEB1-AS1 and miR-299-3p, as well as E2F1 and miR-299-3p. It was demonstrated that, in HCC tissues and cells, ZEB1-AS1 expression was markedly increased, and meanwhile, its high expression level is related to the unfavorable clinicopathologic indicators. ZEB1-AS1 overexpression facilitated HCC cell proliferation, migration and invasion, while its knockdown led to the opposite effects. In terms of mechanism, we discovered that ZEB1-AS1 could decoy miR-299-3p and up-regulate E2F1 expression. This work reveals the functions and mechanism of ZEB1-AS1 in HCC tumorigenesis and progression, which provides novel biomarkers and therapeutic targets for HCC.

scholarly journals CXCL5/NF-κB Pathway as a Therapeutic Target in Hepatocellular Carcinoma Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xingqing Jia ◽  
Shuangqin Wei ◽  
Wujun Xiong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Target Gene ◽  
Underlying Mechanism ◽  
Transwell Assay ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Proliferation And Invasion

Background. Hepatocellular carcinoma (HCC) is a common malignant cancer worldwide. CXCL5 has a role in inhibiting cell viability and metastasis in many tumors. In the present study, we investigated the role of CXCL5 in HCC and explored the underlying mechanism. Material and Methods. RT-qPCR and western blot were performed to evaluate the mRNA and protein levels of CXCL5. CCK-8 and transwell assay were applied to measure the proliferative and invasive abilities. Meanwhile, the Kaplan–Meier method was used to assess the survival of HCC patients. Results. CXCL5 was upregulated in HCC tissues, which predicted a shorter overall survival in HCC. CXCL5 was a target gene of miR-577, and its expression was mediated by miR-577 in HCC. Knockdown of CXCL5 suppressed HuH-7 cell proliferation, invasion, and EMT and inhibited the NF-κB signaling pathway in cells. Moreover, knockdown of CXCL5 inhibited the xenograft growth of HuH-7 cells. Conclusion. Overexpression of CXCL5 predicts poor prognosis in HCC patients. Knockdown of CXCL5 inhibits cell proliferation and invasion through the NF-κB signaling pathway in HCC. The newly identified role of the CXCL5/miR-577/NF-κB axis provides novel insights into the targeted therapy of HCC.

Fbxw11 Variants Promotes Proliferation of Leukemia Cells By Activating the NF-κB Signaling Pathway

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 894-894
Author(s):  
Lina Wang ◽  
Jinfeng Liao ◽  
Wenli Feng ◽  
Xiao Yang ◽  
Shayan Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Leukemia Cells ◽  
Control Group ◽  
Over Expression

Abstract Fbxw11, as a member of F-box proteins family, is a constituent of the SCF (Skp1-Cul1-F box) ubiquitin ligase complex. This ligase ubiquitinates specifically phosphorylated substrates and controls the degradation and half-life of key cellular regulators. So, Fbxw11 play a pivotal role in many aspects of hematopoiesis and tumorigenesis through regulating various signal transduction pathways. We found two transcript variants (Fbxw11c and Fbxw11d) in mouse bone marrow. However the role of Fbxw11 variants in the development of leukemia and the underlying mechanisms remain largely unknown. In this study, we cloned three transcript variants (Fbxw11a, Fbxw11c and Fbxw11d) to study the biological function of Fbxw11 in leukemia. In order to investigate the role of Fbxw11 variants in leukemia, we established L1210 cell lines with over-expression of Fbxw11a, Fbxw11c and Fbxw11d respectively using the lentivirus system. The effect of Fbxw11 variants on proliferation of leukemia cells in vitro was first detected. Growth curve of leukemia cells with Fbxw11a, Fbxw11c or Fbxw11d over-expression was established by cell counting. The results suggested that over-expression of Fbxw11 variants stimulated the growth of leukemia cells. Then MTT experiment was carried out to study the effect of Fbxw11 variants on leukemia cell proliferation and the results showed that Fbxw11 variants increased the proliferation of L1210 cells in vitro. To further confirm the effects of Fbxw11 variants on proliferation of leukemia cells in vivo, tumor xenografts model with over-expression of Fbxw11a, Fbxw11c and Fbxw11d in DBA/2 mice was established. Leukemia cells L1210 with over-expression of Fbxw11a, Fbxw11c and Fbxw11d respectively were transplanted into DBA/2 mice by hypodermic injection. The tumor growth curves showed that tumor growth was increased in Fbxw11 variants over-expression group compared to the control group. Mice were sacrificed on day 28 after transplantation, greater volume of the xenograft tumors were obtained from Fbxw11 variants over-expression group than control group. Therefore, Over-expression of Fbxw11 variants could increase growth of tumor in vivo. To further investigate the molecular mechanism under the effect of Fbxw11 variants on proliferation of leukemia cells, we tested the apoptosis and cell cycle of leukemia cells with Fbxw11 variants over-expression. Over-expression of Fbxw11 variants did not affect the cell apoptosis but accelerated the process of cell cycle. These results revealed that the increased cell proliferation was not due to decrease in cell apoptosis but due to increase in cell cycle. In addition, we tested the effect of Fbxw11 variants on the signal transduction by dual-luciferase reporter gene system. The results showed that over-expression of Fbxw11 variants caused the activation of NF-κB signaling pathway. In conclusion, our findings suggest that Fbxw11 variants have promoting effect on cell proliferation of leukemia cells. The effect of Fbxw11 variants on cell proliferation are due to accelerated the process of cell cycle but not decreasing in cell apoptosis. Further study demonstrated that Fbxw11 variants promote cell proliferation through activating the NF-κB signaling pathway. The important role of Fbxw11 in regulating the development of leukemia suggests that a potent rationale for developing Fbxw11 as a potential therapeutic target against leukemia. Disclosures No relevant conflicts of interest to declare.

Accumulation of AGO2 facilitates tumor proliferation and metastasis through upregulating Survivin, Vimentin and Snail in human hepatocellular carcinoma

2019 ◽  
Author(s):  
Yang Yang ◽  
Qi Mei
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Proliferation And Metastasis ◽  
Interfering Rna ◽  
Cell Proliferation And Metastasis

Abstract Background：Argonaute 2 (AGO2), a typical member of the Ago gene family, plays a pivotal role in hepatocellular carcinoma (HCC) tumorgenesis through regulating the short interfering RNA-mediated gene silencing. However, the underlined mechanism needs clarified. Herein, we found that AGO2 was frequently upregulated in human HCC cancerous tissues compared with non-cancerous tissues. Methods: Clinical analyses were performed to determine the relation between the expression level of AGO2 and prognosis in HCC patients. By using CRISPR/Cas9 approach in SMMC-7721 cells and establishing xenograft model in nude mice, we further identified the role of AGO2 in HCC. Gene expression microarray analysis was used to reveal the changes of gene expression profile mediated by AGO2 depletion in SMMC-7721 cells. Results: We observed that the overexpression of AGO2 was associated with poor prognosis in HCC patients. The knockout of AGO2 inhibited tumor cell proliferation and metastasis in vivo and in vitro. We also identified that AGO2 facilitates HCC tumorigenesis through modulating Survivin, Vimentin and Snail expression. Conclusions: Therefore, this study not only demonstrates that accumulation of AGO2 promotes cell proliferation and metastasis in HCC, but also provides a novel molecular mechanism in HCC progression.

scholarly journals USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Yuning Liao ◽  
Zhenlong Shao ◽  
Yuan Liu ◽  
Xiaohong Xia ◽  
Yuanfei Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Deubiquitinating Enzymes ◽  
Poor Survival ◽  
Clinical Observations ◽  
Inhibition Of Growth ◽  
Proliferation And Metastasis ◽  
Novel Strategy ◽  
Human Hepatocellular Carcinoma Cells

Abstract Background Hepatocellular carcinoma (HCC) remains a medical challenge due to its high proliferation and metastasis. Although deubiquitinating enzymes (DUBs) play a key role in regulating protein degradation, their pathological roles in HCC have not been fully elucidated. Methods By using biomass spectrometry, co-immunoprecipitation, western blotting and immunofluorescence assays, we identify ribosomal protein S16 (RPS16) as a key substrate of ubiquitin-specific peptidase 1 (USP1). The role of USP1-RPS16 axis in the progression of HCC was evaluated in cell cultures, in xenograft mouse models, and in clinical observations. Results We show that USP1 interacts with RPS16. The depletion of USP1 increases the level of K48-linked ubiquitinated-RPS16, leading to proteasome-dependent RPS16 degradation. In contrast, overexpression of USP1-WT instead of USP1-C90A (DUB inactivation mutant) reduces the level of K48-linked ubiquitinated RPS16, thereby stabilizing RPS16. Consequently, USP1 depletion mimics RPS16 deficiency with respect to the inhibition of growth and metastasis, whereas transfection-enforced re-expression of RPS16 restores oncogenic-like activity in USP1-deficient HCC cells. Importantly, the high expression of USP1 and RPS16 in liver tissue is a prognostic factor for poor survival of HCC patients. Conclusions These findings reveal a previously unrecognized role for the activation of USP1-RPS16 pathway in driving HCC, which may be further developed as a novel strategy for cancer treatment.

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