scholarly journals MiR-27a-3p enhances the cisplatin sensitivity in hepatocellular carcinoma cells through inhibiting PI3K/Akt pathway

2021 ◽  
Author(s):  
Ying Yang ◽  
Zhifang Yang ◽  
Ruili Zhang ◽  
Chunli Jia ◽  
Rui Mao ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Suppressor Gene ◽  
Carcinoma Cells ◽  
Akt Signaling Pathway ◽  
Apoptosis Rate ◽  
Favorable Prognosis ◽  
Tumor Tissues ◽  
Cisplatin Sensitivity ◽  
Prognosis Indicator ◽  
The Relationship

MicroRNAs (miRNAs) play an important role in drug-resistance, and it’s reported that MiR-27a-3p regulated the sensitivity of cisplatin in breast cancer, lung cancer and ovarian cancer. However, the relationship between miR-27a-3p and chemosensitivity of cisplatin in HCC was unclear, especially the underlying mechanism was unknown. In present study, we analyzed miR-27a-3p expression levels in 372 tumor tissues and 49 adjacent tissues in HCC samples from TCGA database, and found that the miR-27a-3p was downregulated in HCC tissues. The level of miR-27a-3p was associated with metastasis, Child-Pugh grade and race. MiR-27a-3p was regarded as a favorable prognosis indicator for HCC patients. Then, miR-27a-3p was overexpressed in HepG2 cell, and was knockdown in PLC cell. Next, we conducted a series of vitro assays, including MTT, apoptosis and cell cycle assays to observe the biological changes. Further, inhibitor rate and apoptosis rate were detected with pre- and post-cisplatin treatment in HCC. The results showed that overexpression of miR-27a-3p repressed the cell viability, promoted apoptosis and increased the percentage of cells in phase G0/G1 phase. Importantly, overexpression of miR-27a-3p significantly increased the inhibitor rate and apoptosis rate with cisplatin intervention. Besides, we found that miR-27a-3p added cisplatin sensitivity potentially through regulating PI3K/Akt signaling pathway. Taken together, MiR-27a-3p acted as a tumor suppressor gene in HCC cells, and it could be useful for modulating cisplatin sensitivity in chemotherapy therapy

scholarly journals Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Chi Square ◽  
Tumor Tissues ◽  
The Relationship ◽  
Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

scholarly journals Sirt1 deacetylates and stabilizes p62 to promote hepato-carcinogenesis

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Lifeng Feng ◽  
Miaoqin Chen ◽  
Yiling Li ◽  
Muchun Li ◽  
Shiman Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cell Growth ◽  
Knockout Mice ◽  
Liver Tumors ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Conditional Knockout

Abstractp62/SQSTM1 is frequently up-regulated in many cancers including hepatocellular carcinoma. Highly expressed p62 promotes hepato-carcinogenesis by activating many signaling pathways including Nrf2, mTORC1, and NFκB signaling. However, the underlying mechanism for p62 up-regulation in hepatocellular carcinoma remains largely unclear. Herein, we confirmed that p62 was up-regulated in hepatocellular carcinoma and its higher expression was associated with shorter overall survival in patients. The knockdown of p62 in hepatocellular carcinoma cells decreased cell growth in vitro and in vivo. Intriguingly, p62 protein stability could be reduced by its acetylation at lysine 295, which was regulated by deacetylase Sirt1 and acetyltransferase GCN5. Acetylated p62 increased its association with the E3 ligase Keap1, which facilitated its poly-ubiquitination-dependent proteasomal degradation. Moreover, Sirt1 was up-regulated to deacetylate and stabilize p62 in hepatocellular carcinoma. Additionally, Hepatocyte Sirt1 conditional knockout mice developed much fewer liver tumors after Diethynitrosamine treatment, which could be reversed by the re-introduction of exogenous p62. Taken together, Sirt1 deacetylates p62 at lysine 295 to disturb Keap1-mediated p62 poly-ubiquitination, thus up-regulating p62 expression to promote hepato-carcinogenesis. Therefore, targeting Sirt1 or p62 is a reasonable strategy for the treatment of hepatocellular carcinoma.

scholarly journals RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ying-Ying Liang ◽  
Xu-Bin Deng ◽  
Xian-Tao Lin ◽  
Li-Li Jiang ◽  
Xiao-Ting Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Transcriptional Coactivator ◽  
Actin Remodeling ◽  
Aggressive Tumor ◽  
Subunit B

Abstract Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.

Consumers Complain More Fiercely Through Small-Screen Devices: The Role of Spatial Crowding Perception

2020 ◽  
Vol 23 (3) ◽  
pp. 353-367
Author(s):  
Yuanyuan Zhou ◽  
Bin Tian ◽  
Tingting Mo ◽  
Zhuoying Fei
Keyword(s):  
Secondary Data ◽  
Underlying Mechanism ◽  
Screen Size ◽  
Design Elements ◽  
Perception Theory ◽  
Fourth Experiment ◽  
Complaint Behavior ◽  
The Relationship ◽  
Small Screen

Previous research has mainly focused on the determinants of consumers’ complaint channel choices. Little attention has been paid to the behavioral consequences of different complaint channels, particularly different complaint devices. Drawing on spatial crowding perception theory, this study finds that in an online complaint context, consumers’ complaint intensity is shaped by complaint devices that differ in screen size. Crowding perception produced by visually restrictive tension mediates the relationship between the screen size of the complaint device and the complaint intensity. The results of secondary data confirm that consumers’ complaint intensity is higher while complaining through a small-screen device (as opposed to a large-screen one). Three scenario-based experiments are conducted to examine the role of perceived spatial crowding in producing a more intense complaint behavior when complaints are submitted through smaller screen devices (as opposed to larger screen devices). The fourth experiment reveals that crowding perception can be lessened by adjusting certain design elements of the interface, ultimately mitigating the intensity of the complaint submitted through a small-screen device. Our research identifies the specific causality and underlying mechanism of the influence of device type on consumers’ postconsumption behavior, thus contributing to clarify some ambiguities in the literature.

scholarly journals DNA-Bound Platinum Is the Major Determinant of Cisplatin Sensitivity in Head and Neck Squamous Carcinoma Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61555 ◽  
Author(s):  
Sanne R. Martens-de Kemp ◽  
Simone U. Dalm ◽  
Fiona M. J. Wijnolts ◽  
Arjen Brink ◽  
Richard J. Honeywell ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Carcinoma ◽  
Carcinoma Cells ◽  
Major Determinant ◽  
Squamous Carcinoma Cells ◽  
Cisplatin Sensitivity

scholarly journals Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells

2016 ◽  
Vol 242 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Guanghui Cui ◽  
Donglei Liu ◽  
Weihao Li ◽  
Yuhang Li ◽  
Youguang Liang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Prediction ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Original Research ◽  
Proliferation And Invasion

Increasing evidence suggests that miR-194 is down-regulated in esophageal squamous cell carcinoma tumor tissue. However, the role and underlying mechanism of miR-194 in esophageal squamous cell carcinoma have not been well defined. We used DIANA, TargetScan and miRanda to perform target prediction analysis and found KDM5B is a potential target of miR-194. Based on these findings, we speculated that miR-194 might play a role in esophageal squamous cell carcinoma development and progression by regulation the expression of KDM5B. We detected the expression of miR-194 and KDM5B by quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays, respectively, and found down-regulation of miR-194 and up-regulation of KDM5B existed in esophageal squamous cell carcinoma cell lines. By detecting proliferation, invasion and apoptosis of TE6 and TE14 cells transfected with miR-194 mimics or mimic control, miR-194 was found to inhibit proliferation and invasion and promote apoptosis of esophageal squamous cell carcinoma cells. miR-194 was further verified to regulate proliferation, apoptosis and invasion of esophageal squamous cell carcinoma cells by directly targeting KDM5B. Furthermore, animal studies were performed and showed that overexpression of miR-194 inhibited the growth of esophageal squamous cell carcinoma tumors in vivo. These results confirmed our speculation that miR-194 targets KDM5B to inhibit esophageal squamous cell carcinoma development and progression. These findings offer new clues for esophageal squamous cell carcinoma development and progression and novel potential therapeutic targets for esophageal squamous cell carcinoma.

Mediating Effect of WhatsApp Addiction Between Social Loneliness and Preference for Online Social Interaction: A Cross-cultural Study

2021 ◽  
pp. 097215092110556
Author(s):  
Komal Nagar ◽  
Gurmeet Singh ◽  
Rabinder Singh
Keyword(s):  
Social Interaction ◽  
Underlying Mechanism ◽  
Mediating Effect ◽  
Mediating Role ◽  
Cross Cultural Study ◽  
Online Social Interaction ◽  
The Relationship ◽  
Moderating Role ◽  
Social Loneliness

The present study aims to explore the relationship between social loneliness and online interaction through WhatsApp addiction among a sample of Indian and Fijian respondents. Based on the responses of 202 Indian and 73 Fijian respondents, the present research study validated the mediating role of WhatsApp addiction, revealing that social loneliness increased the possibility of preferring to interact online through increased WhatsApp addiction. The empirical results showed that the underlying mechanism of social loneliness might indirectly influence consumers’ preference for online social interaction (POSI). The study further assessed the moderating role of culture in the association between social loneliness and POSI. Findings of the moderated mediation analysis demonstrated that, the association between loneliness and preference to socialize online differed, based on the identified cultural differences between Indian and Fijian groups.

Tapping the Power of Social Media on Innovation Performance

2021 ◽  
Vol 9 (2) ◽  
pp. 143-151
Author(s):  
Shan Shan Teh ◽  
Daisy Mui Hung Kee ◽  
Munazza Zahra ◽  
Gadi Dung Paul
Keyword(s):  
Social Media ◽  
Data Collection ◽  
Open Innovation ◽  
Underlying Mechanism ◽  
Jel Classification ◽  
Innovation Performance ◽  
Great Idea ◽  
New Evidence ◽  
The Relationship ◽  
Innovation Impact

Objective - This study investigates the relationship between social media and innovation performance among SMEs in Malaysia. This study also extends social media literature by investigating the underlying mechanism of open innovation in the relationship between social media and innovation performance. Methodology/Technique - A questionnaire was used to collect data from the respondents. A total of 173 samples from data collection were then used to test the hypotheses by using the SPSS and SmartPLS software. Finding - The result has revealed that social media has a significant effect on innovation performance. Besides, outbound innovation is also found to mediate the relationship between social media and innovation performance. Novelty - This study contributes to the literature on social media and innovation by providing new evidence regarding outbound innovation impact on performance among SMEs. It also provides a great idea of social media's importance to SME managers in improving innovation performance in an organization. Type of Paper - Empirical. Keywords: Social Media, Innovation Performance, Open Innovation, Smes, Malaysia JEL Classification: URI: http://gatrenterprise.com/GATRJournals/GJBSSR/vol9.2_4.html DOI: https://doi.org/10.35609/gjbssr.2021.9.2(4) Pages 143 – 151

scholarly journals KLF2 Inhibits the Migration and Invasion of Prostate Cancer Cells by Downregulating MMP2

2018 ◽  
Vol 13 (1) ◽  
pp. 155798831881690 ◽  
Author(s):  
Binshuai Wang ◽  
Mingyuan Liu ◽  
Yimeng Song ◽  
Changying Li ◽  
Shudong Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cell Function ◽  
Malignant Tumors ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Tumor Tissues ◽  
Luciferase Activity Assay

KLF2, a member of the Kruppel-like factor (KLF) family, is thought to be a tumor suppressor in many kinds of malignant tumors. Its functions in prostate cancer (PCa) are unknown. This study aimed to explore the role of KLF2 in the migration and invasion of PCa cells. The expression of KLF2 was measured by immunohistochemistry in PCa tissues and in paired non-tumor tissues. KLF2 and MMP2 expression in cells was measured by Western blot and RT-qPCR. Adenoviruses and siRNAs were used in cell function tests to investigate the role of KLF2 in regulating MMP2. Interactions between KLF2 and MMP2 were analyzed by a luciferase activity assay. The present study, for the first time, identified that KLF2 was downregulated both in PCa clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2.This study demonstrates that KLF2 might act as a tumor suppressor gene in PCa and that the pharmaceutical upregulation of KLF2 may be a potential approach for treatment.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

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