scholarly journals Nucleobindin-2/Nesfatin-1—A New Cancer Related Molecule?

2021 ◽  
Vol 22 (15) ◽  
pp. 8313
Author(s):  
Alicja M. Kmiecik ◽  
Piotr Dzięgiel ◽  
Marzenna Podhorska-Okołów
Keyword(s):  
Cancer Progression ◽  
Treatment Options ◽  
Predictive Marker ◽  
Clinicopathological Characteristics ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Ovarian Epithelial Carcinoma ◽  
Treatment Responses ◽  
Poor Outcomes ◽  
Prognostic And Predictive Markers

Cancer is a heterogeneous disease, and even tumors with similar clinicopathological characteristics show different biology, behavior, and treatment responses. As a result, there is an urgent need to define new prognostic and predictive markers to make treatment options more personalized. According to the latest findings, nucleobindin-2/nesfatin-1 (NUCB2/NESF-1) is an important factor in cancer development and progression. Nucleobindin-2 is a precursor protein of nesfatin-1. As NUCB2 and nesfatin-1 are colocalized in each tissue, their expression is often analyzed together as NUCB2. The metabolic function of NUCB2/NESF-1 is related to food intake, glucose metabolism, and the regulation of immune, cardiovascular and endocrine systems. Recently, it has been demonstrated that high expression of NUCB2/NESF-1 is associated with poor outcomes and promotes cell proliferation, migration, and invasion in, e.g., breast, colon, prostate, endometrial, thyroid, bladder cancers, or glioblastoma. Interestingly, nesfatin-1 is also considered an inhibitor of the proliferation of human adrenocortical carcinoma and ovarian epithelial carcinoma cells. These conflicting results make NUCB2/NESF-1 an interesting target of study in the context of cancer progression. The present review is the first to describe NUCB2/NESF-1 as a new prognostic and predictive marker in cancers.

JAK2 variations and functions in lung adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23181-e23181
Author(s):  
Xu Yanjun ◽  
Fan Yun
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Treatment Options ◽  
Jak2 V617f ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Pathogenesis

e23181 Background: Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains extremely low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers, including lung cancer. Recently we found that JAK2 might play an important role in lung cancer pathogenesis as an oncogene. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the activities of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients. Methods: The expression level of JAK2 mRNA was assayed using RT-PCR. JAK2 mutations and amplification were detected using next-generation sequencing (NGS). MTT assay, Transwell migration and invasion assay were conducted to study the proliferation, migration and invasion abilities of lung adenocarcinoma cells independently. The shRNA and overexpression plasmids of JAK2 were conducted. Results: JAK2 is up-regulated in lung adenocarcinoma tissues when compared with their adjacent non-tumor tissues, and was associated with lymph node metastasis ( p< 0.05). JAK2 V617F and N30S mutations and JAK2 amplification were detected by NGS in lung adenocarcinoma patient samples. Downregulation of JAK2 inhibits the proliferation, migration and invasion abilities of lung cancer cells. Moreover, overexpression of JAK2 induced the proliferation, migration and invasion abilities of lung cancer cells. Conclusions: These findings demonstrate that JAK2, whose expression is up-regulated in lung adenocarcinoma, whose mutation and amplification were detected in lung adenocarcinoma, may participate in lung cancer progression by regulating cancer cells proliferation, migration and invasion.

scholarly journals PDE4B Induces Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Is Transcriptionally Suppressed by CBX7

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhengnan Huang ◽  
Jiakuan Liu ◽  
Jiale Yang ◽  
Yilin Yan ◽  
Chenkai Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Ectopic Expression ◽  
Urinary Bladder Cancer ◽  
Clinicopathological Characteristics ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Functional Studies ◽  
Poor Outcomes

Urinary bladder cancer (UBC) is a common malignant tumor with high incidence. Advances in the diagnosis and treatment of this disease demand the identification of novel therapeutic targets. Multiple studies demonstrated that PDE4B level was upregulated in malignancies and high PDE4B expression was correlated with poor outcomes. Herein, we identified that PDE4B was a potential therapeutic target in UBC. We confirmed that PDE4B expression was correlated with aggressive clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ectopic expression of PDE4B promoted UBC cells proliferation, migration and invasion, whereas PDE4B depletion suppressed cancer cell aggressiveness. We also identified CBX7 as a regulator of PDE4B to suppress the expression of PDE4B at the transcription level in a PRC1-dependent manner. Moreover, our results indicated that PDE4B induced epithelial-to-mesenchymal transition (EMT) in UBC cells via β-catenin pathway, whereas inhibition of PDE4B by its small molecule inhibitor, rolipram, effectively reversed the PDE4B overexpression-induced effects. To sum up, our results indicated that PDE4B acts as an oncogene by promoting UBC cell migration and invasion via β-catenin/EMT pathway.

scholarly journals The Integrated Analysis of Differential Long Non-Coding RNAs Expression Profiles in Extracellular Vesicles Derived From Chemoradioresistant and Parental Nasopharyngeal Carcinoma Cells

2021 ◽  
Author(s):  
Wei Xiong ◽  
Runmei Sun ◽  
Chunyan Li ◽  
Cheng Li ◽  
Jiyong Qin ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Human Cancer ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Transmission Electron ◽  
Non Coding Rnas ◽  
Poor Outcomes

Abstract The patients with nasopharyngeal carcinoma (NPC) suffer from poor outcomes after chemoradiotherapy. Extracellular vesicles (EVs) play crucial roles in regulating cancer progression and chemoradioresistance. To investigate the functional role of chemoradioresistant cell-derived EVs for parental cells, and long non-coding RNAs (lncRNAs) expression profiles in EVs secreted by chemoradioresistant cells. The effect of chemoradioresistant NPC cell-derived EVs on migration and invasion abilities of parental cells were detected by Transwell assays. Human cancer lncRNA PCR array was performed on EVs released from chemoradioresistant NPC cells (CNE1R and CNE2R) and parental cells (CNE1 and CNE2). The concurrent chemoradioresistance of CNE1R and CNE2R was significant higher than that of CNE1 and CNE2. Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blotting results showed the CNE1, CNE2, CNE1R and CNE2R -derived EVs were successfully obtained. The chemoradioresistant cell-derived EVs remarkably promoted migration and invasion ability of parental cells with different differentiation. Notably, a total of 91 differentially expressed (DE) lncRNAs were regulated in EVs by chemoradiotherapy. Among them, the 4 upregulated (MALAT1, FAM212B-AS1, LINC-PINT and H19) and 7 down-regulated (SNHG16, CDKN2B-AS1, ZFAS1, CCAT1, SNHG6, GAPLINC and TUG1) DE lncRNAs associated with chemoradioresistance, were identified in EVs derived from chemoradioresistant cells with different differentiation. We found the EVs derived from chemoradioresistant NPC cells regulated an aggressive phenotype of NPC cells, and identified an altered lncRNAs expression pattern in chemoradioresistant NPC cell- derived EVs.

scholarly journals NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Yuanbo Hu ◽  
Chenbin Chen ◽  
Xinya Tong ◽  
Sian Chen ◽  
Xianjing Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Treatment Options ◽  
Biological Significance ◽  
Tissue Microarrays ◽  
Migration And Invasion ◽  
Multiple Cancer ◽  
Carcinogenic Activity

AbstractThe 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

Overexpression of p62 Induces Autophagy and Promotes Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma Cells through Promoting ERK Signaling Pathway

2020 ◽  
Vol 20 (8) ◽  
pp. 624-637 ◽  
Author(s):  
Qiong Wu ◽  
Manlin Xiang ◽  
Kun Wang ◽  
Zhen Chen ◽  
Lu Long ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Clinical Analysis ◽  
Carcinoma Cells ◽  
Immunofluorescent Staining ◽  
Clinicopathological Parameters ◽  
Migration And Invasion ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Potential Biomarker

Background: Increasing evidence has shown that p62 plays an important role in tumorigenesis. However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated. Objective: To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma. Methods: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters. Results: We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal-regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P<0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis. Conclusion : Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC.

Cancer Fighting SiRNA-RRM2 Loaded Nanorobots

2020 ◽  
Vol 8 (2) ◽  
pp. 79-90
Author(s):  
Arjun Sharma ◽  
Pravir Kumar ◽  
Rashmi K. Ambasta
Keyword(s):  
Cancer Therapy ◽  
Dna Synthesis ◽  
Cancer Progression ◽  
Sirna Delivery ◽  
Predictive Marker ◽  
The Body ◽  
Tumor Site ◽  
Target Delivery ◽  
Target Effect

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

scholarly journals A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raymond J. Langley ◽  
Marie E. Migaud ◽  
Lori Flores ◽  
J. Will Thompson ◽  
Elizabeth A. Kean ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Patient Outcomes ◽  
Medical Intensive Care Unit ◽  
Close Association ◽  
Treatment Options ◽  
Feature Model ◽  
High Morbidity ◽  
Medical Intensive Care ◽  
Poor Outcomes

AbstractAcute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.

Sign in / Sign up

Export Citation Format

Share Document