scholarly journals LncRNA SNHG8 Promotes Liver Cancer Proliferation and Metastasis by Sponging miR-542-3p and miR-4701-5p

2021 ◽  
Author(s):  
He Tong ◽  
Shuang He ◽  
Kexin Li ◽  
qirile Sa ◽  
Kefan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Cancer Proliferation ◽  
Competing Endogenous Rnas ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Nucleolar Rna

Abstract Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs). LncRNA small nucleolar RNA host gene 8 (LncRNA SNHG8) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the molecular mechanisms by which lncRNA SNHG8 contributes to hepatocellular carcinoma (HCC) still remains unclear. In the present study, we reported that lncRNA SNHG8 was abnormally up-regulated in liver cancer tissues and HCC cell lines. Moreover, knockdown of lncRNA SNHG8 significantly attenuated the proliferation, migration, invasion process of HCC cell line HepG2 in vitro. Mechanistically, we first reported that suppression of lncRNA SNHG8 evidently enhanced miR-542-3p and miR-4701-5p expression and decreased TET3 expression at posttranscriptional level. Furthermore, lncRNA SNHG8 upregulated TET3 expression by sponging miR-542-3p and miR-4701-5p by competing binding. Taken together, our results confirmed the oncogene role of lncRNA SNHG8 and discovered the underlying mechanism that lncRNA SNHG8 upregulated TET3 through the sponging or decaying of miR-542-3p and miR-4701-5p in human hepatocellular carcinoma, suggesting that lncRNA SNHG8 may serve as a potential diagnostic marker and therapeutic target for patients with hepatocellular carcinoma.

scholarly journals miR-183-5p promotes proliferation and migration in hepatocellular carcinoma by targeting IRS1 and its association with patient survival

2020 ◽  
Vol 35 (3) ◽  
pp. 83-89
Author(s):  
Rong Yan ◽  
Kang Li ◽  
Dawei Yuan ◽  
Haonan Wang ◽  
Wei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Progression ◽  
Normal Tissues ◽  
Report Analysis ◽  
In Vitro Effects ◽  
And Migration ◽  
Cancer Tissues ◽  
Proliferation And Migration

Background: MiR-183-5p plays an important role in the pathophysiology of many tumors, while the role of MiR-183-5p in liver cancer is unclear. Methods: In this study, quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect the expression of miR-183-5p in liver cancer cell lines, liver cancer tissues, and normal tissues adjacent to the cancer, and to explore the mechanism of miR-183-5p regulating liver cancer progression. The in vitro effects of miR-183-5p were evaluated by CCK-8, colony formation test, and wound healing test. Various databases were used to predict the target mRNA of miR-183-5p and verified by luciferase report analysis. In addition, the effects of miR-183-5p and its target gene on the survival of patients with liver cancer were also analyzed. Results: miR-183-5p was highly expressed in hepatocellular carcinoma cells and tissues, and was related to some clinicopathological features. MiR-183-5p can promote the proliferation and migration of liver cancer cells. Using the bioinformatics database, we proved that miR-183-5p is related to the survival of liver cancer patients. Insulin receptor substrate 1 (IRS1) is a target of miR-183-5p, and luciferase analysis confirmed that miR-183-5p combines with the 3′-untranslated region (3′-UTR) of IRS1. Conclusion: The miR-183-5p/IRS1 axis may be a new target for liver cancer research.

scholarly journals Targeting TRIM54/Axin1/β-Catenin Axis Prohibits Proliferation and Metastasis in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinrong Zhu ◽  
Yongqi Wu ◽  
Shaoxi Lao ◽  
Jianfei Shen ◽  
Yijian Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factor ◽  
Small Molecule ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Proliferation And Metastasis ◽  
Oncogenic Gene ◽  
Sustained Activation

Accumulating evidence demonstrates that dysregulation of ubiquitin-mediated degradation of oncogene or suppressors plays an important role in several diseases. However, the function and molecular mechanisms of ubiquitin ligases underlying hepatocellular carcinoma (HCC) remain elusive. In the current study, we show that overexpression of TRIM54 was associated with HCC progression. TRIM54 overexpression facilitates proliferation and lung metastasis; however, inhibition of TRIM54 significantly suppressed HCC progression both in vitro and in vivo. Mechanically, we demonstrated that TRIM54 directly interacts with Axis inhibition proteins 1 (Axin1) and induces E3 ligase-dependent proteasomal turnover of Axin1 and substantially induces sustained activation of wnt/β-catenin in HCC cell lines. Furthermore, we showed that inhibition of the wnt/β-catenin signaling pathway via small molecule inhibitors significantly suppressed TRIM54-induced proliferation. Our data suggest that TRIM54 might function as an oncogenic gene and targeting the TRIM54/Axin1/β-catenin axis signaling may be a promising prognostic factor and a valuable therapeutic target for HCC.

scholarly journals Telocytes Promote the Metastasis of Hepatocellular Carcinoma by Activating ERK Signaling Pathway and Sponging miR-942-3p to Impact MMP9

2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Cancer Tissue ◽  
Proliferative Potential ◽  
Cancer Tissues ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma(HCC) in China is considered as a familiar malignant tumor with poor prognosis, high metastasis and disease relapse. Telocytes(TCs) have been verified to participate in progresses of tumorigenesis, invasions and migrations by secreting functional proteins and transmitting cell-to-cell information. Extracellular signal-regulared protein kinase(ERK) signal pathway is a vital mechanism driving cell proliferation, metastasis and apoptosis, but whether this molecular signaling mechanism contributes to matrix metalloproteinase-9(MMP) expression of TCs remains unclear. Methods: Telocytes and MMP9 expression in the liver cancer tissues are measured by immunohistochemistry assay, Westen blot assay and RT-PCR technique, meanwhile primary telocytes from liver para-cancer tissues are cultured in vitro. To demonstrate the function of telocytes for hepatocellular carcinoma, the metastatic cancer animal model is established by three typs of liver cancer cell-lines in vivo. Results: In our study, we elucidate that TCs in the para-cancer tissue can promote the metastasis of HCC cells by MMP-9 expression, in vitro and in vivo. PDGF derived from HCC cells has a capacity to activate Ras/ERK signaling pathway of TC as a result of accelerating MMP-9 expression, but it’s no significant for proliferative potential and apoptotic rate of TCs. While tyrosine kinase inhibitors and miR-942-3p suppress MMP-9 expression to make loss functions of TCs. Various mutations of TCs are also tested and single nucleotide polymorphisms of MMP-9 may be the potentially molecular mechanism of increasing protein expression in the invasive process of HCC. Conclusion: Our results demonstrate two potential mechanisms between HCC cells and TCs, suggesting that TC is a novel marker and target on deciphering reasons of cancer metastasis.

Telocytes Promote Hepatocellular Carcinoma by Activating The ERK Signaling Pathway and miR-942-3p/MMP9 Axis

2021 ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
Peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Metastatic Cancer ◽  
Erk Signaling ◽  
Mmp9 Expression ◽  
Cancer Tissues

Abstract Background In China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but theirs functions in HCC are still unknown. Methods TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using 3 types of liver cancer cell lines in vivo. Results TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; however, this had no significant effect on TC proliferation and apoptosis. miR-942-3p suppressed MMP9 expression in TCs. Conclusion Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC.

scholarly journals LncRNA RP11-295G20.2 regulates hepatocellular carcinoma cell growth and autophagy by targeting PTEN to lysosomal degradation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Linhui Liang ◽  
Lin Huan ◽  
Jiajia Wang ◽  
Yangjun Wu ◽  
Shenglin Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lysosomal Degradation ◽  
Pten Protein ◽  
Pten Loss ◽  
Liver Cancer Cells ◽  
Therapeutic Benefits

AbstractPTEN is a crucial tumor suppressor and loss of PTEN protein is involved in various cancers. However, the detailed molecular mechanisms of PTEN loss in cancers remain elusive, especially the involvement of lncRNAs. Here, lncRNA RP11-295G20.2 is found to be significantly upregulated in hepatocellular carcinoma (HCC) and promotes the growth of liver cancer cells both in vitro and in vivo. Furthermore, RP11-295G20.2 inhibits autophagy in liver cancer cells. Interestingly, RP11-295G20.2 directly binds to the PTEN protein and leads to its degradation. RP11-295G20.2 expression is inversely correlated with PTEN protein expression in 82 TCGA/TCPA-LIHC samples. Surprisingly, RP11-295G20.2-induced PTEN degradation occurs through the lysosomal pathway instead of the proteasome pathway. RP11-295G20.2 binds to the N terminus of PTEN and facilitates the interaction of p62 with PTEN. Thus, PTEN is translocated into lysosomes and degraded. RP11-295G20.2 also influences AKT phosphorylation and forkhead box O 3a (FOXO3a) translocation into the nucleus, in turn regulating the transcription of autophagy-related genes. Collectively, RP11-295G20.2 directly binds to PTEN and enables its lysosomal degradation. This newly identified RP11-295G20.2/PTEN axis reveals an unexplored molecular mechanism regarding PTEN loss in liver cancer and might provide new therapeutic benefits for liver cancer patients.

scholarly journals IL-2 Increases Tams-Derived Exosomal Mir-375 to Ameliorate Hepatocellular Carcinoma Development and Progression

2021 ◽  
Author(s):  
Hao Chen ◽  
Chao Tang ◽  
Fei Wu ◽  
Linming Lu ◽  
Shu Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interleukin 2 ◽  
Clinical Value ◽  
Proliferation And Metastasis ◽  
New Perspective ◽  
Cancer Tissues ◽  
Apoptotic Effects ◽  
Hcc Cells

Abstract Background: Interleukin-2 (IL-2) is proved to play an irreplaceable role in anti-tumor regulation in numerous experimental and clinical trials. Tumor-associated macrophages (TAMs) is able to release exosomes to promote the development and progression of hepatocellular carcinoma (HCC) as part of microenvironment.Methods: In this study, our intention is to explore the effects of the exosomes from TAMs with IL-2 treatment on HCC development.TAMs were collected and cultured from liver cancer tissues. The exosomes from the TAMs treated with IL-2 (ExoIL2-TAM) or not (ExoTAM) were identified and used to treat HCC cells. The HCC cells proliferation, apoptosis and metastasis were measured in vivo and in vitro. The changes of miR-375 in exosomes was explored to clarify whether it is reponsible to the anti-apoptotic effects of IL-2. Results: Both decrease of cell proliferation and metastasis and increase of apoptosis were observed with ExoIL2-TAM treatment compared with ExoTAM in vivo and in vitro. miR-375 was obviously abundant in ExoIL2-TAM. Enriched miR-375 could be transmitted between TAMs and HCC cells via exosomes and was responbible for the increased apoptosis of HCC cells. Conclusions: Taken together, IL-2 increases exosomal miR-375 from TAMs to attenuate hepatocellular carcinoma development. This study provides a new perspective to explain the mechanism how IL-2 inhibits hepatocellular carcinoma and implys the potential clinical value of exosomal miR-375 released by TAMs.

scholarly journals Telocytes promote hepatocellular carcinoma by activating the ERK signaling pathway and miR-942-3p/MMP9 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ying Xu ◽  
Hu Tian ◽  
Chao Guang Luan ◽  
Kai Sun ◽  
Peng Jin Bao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Metastatic Cancer ◽  
Erk Signaling ◽  
Mmp9 Expression ◽  
Cancer Tissues

AbstractIn China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes (TCs) participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but their functions in HCC are still unknown. TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using three types of liver cancer cell lines in vivo. TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet-derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; Moreover, miR-942-3p suppressed MMP9 expression in TCs. Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC.

scholarly journals Long non-coding RNA MIR200CHG promotes breast cancer proliferation, invasion, and drug resistance by interacting with and stabilizing YB-1

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Li Tang ◽  
Da Wei ◽  
Xinyu Xu ◽  
Xuelian Mao ◽  
Dongping Mo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Cancer Proliferation ◽  
In Vivo Experiments ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Cancer Tissues

AbstractLong non-coding RNAs (lncRNA) have been identified as key regulators of tumorigenesis and development. We aim to explore the biological functions and molecular mechanisms of lncRNA MIR200CHG in breast cancer. We found that MIR200CHG is highly expressed in breast cancer tissues and is related to the tumor size and histopathological grade. In vitro and in vivo experiments confirmed that MIR200CHG can promote breast cancer proliferation, invasion, and drug resistance. MIR200CHG directly binds to the transcription factor Y-box binding protein-1 (YB-1), and inhibits its ubiquitination and degradation. MIR200CHG regulates YB-1 phosphorylation at serine 102, thereby affecting the expression of genes related to tumor cell proliferation, apoptosis, invasion, and drug resistance. Additionally, MIR200CHG partially affects the expression of miR-200c/141-3p encoded by its intron region. Therefore, MIR200CHG can promote the proliferation, invasion, and drug resistance of breast cancer by interacting with and stabilizing YB-1, and has the potential to become a target for breast cancer treatment.

Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

2020 ◽  
Vol 16 (1) ◽  
pp. 85-89
Author(s):  
Mahesh M. Gouda ◽  
Ashwini Prabhu ◽  
Varsha Reddy S.V. ◽  
Rafa Jahan ◽  
Yashodhar P. Bhandary
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Plasminogen Activator Inhibitor ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Alveolar Epithelial Cells ◽  
Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

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