scholarly journals COX5B-Mediated Bioenergetic Alterations Modulate Cell Growth and Anticancer Drug Susceptibility by Orchestrating Claudin-2 Expression in Colorectal Cancers

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 60
Author(s):  
Yu-De Chu ◽  
Siew-Na Lim ◽  
Chau-Ting Yeh ◽  
Wey-Ran Lin
Keyword(s):  
Cell Growth ◽  
Anticancer Drugs ◽  
Disease Free Survival ◽  
Postoperative Outcome ◽  
Drug Susceptibility ◽  
Colorectal Cancers ◽  
Expression Ratio ◽  
Cell Behaviors ◽  
Potential Biomarker ◽  
Junction Protein

Oxidative phosphorylation (OXPHOS) consists of four enzyme complexes and ATP synthase, and is crucial for maintaining physiological tissue and cell growth by supporting the main bioenergy pool. Cytochrome c oxidase (COX) has been implicated as a primary regulatory site of OXPHOS. Recently, COX subunit 5B (COX5B) emerged as a potential biomarker associated with unfavorable prognosis by modulating cell behaviors in specific cancer types. However, its molecular mechanism remains unclear, particularly in colorectal cancers (CRCs). To understand the role of COX5B in CRCs, the expression and postoperative outcome associations using independent in-house patient cohorts were evaluated. A higher COX5B tumor/nontumor expression ratio was associated with unfavorable clinical outcomes (p = 0.001 and 0.011 for overall and disease-free survival, respectively. In cell-based experiments, the silencing of COX5B repressed cell growth and enhanced the susceptibility of CRCs cells to anticancer drugs. Finally, downstream effectors identified by RNA sequencing followed by RT-qPCR and functional compensation experiments revealed that the tight junction protein Claudin-2 (CLDN2) acts downstream of COX5B-mediated bioenergetic alterations in controlling cell growth and the sensitivity to anticancer drugs in CRCs cells. In conclusion, it was found that COX5B promoted cell growth and attenuated anticancer drugs susceptibility in CRCs cells by orchestrating CLDN2 expression, which may contribute to unfavorable postoperative outcomes of patients with CRCs.

Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Tumor Immunology ◽  
Bioinformatics Analysis ◽  
Human Cancer ◽  
Disease Free Survival ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

scholarly journals Prognostic Impact of MITD1 and Associates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110362
Author(s):  
Chujie Chen ◽  
Yiyu Sheng
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Functional Enrichment ◽  
Prognostic Impact ◽  
Clinical Value ◽  
Immune Infiltration ◽  
Potential Biomarker

Kidney renal clear cell carcinoma (KIRC) is one of the most malignant diseases with poor survival rate over the world. The tumor microenvironment (TME) is highly related to the oncogenesis, development, and prognosis of KIRC. Thus, making the identification of KIRC biomarkers and immune infiltrates critically important. Microtubule Interacting and Trafficking Domain containing 1(MITD1) was reported to participate in cytokinesis of cell division. In the present study, multiple bioinformatics tools and databases were applied to investigate the expression level and clinical value of MITD1 in KIRC. We found that the expression of MITD1 was significantly increased in KIRC tissues. Further, the KIRC patients with high MITD1 levels showed a worse overall survival (OS) rate and disease free survival (DFS) rate. Otherwise, we found a significant correlation MITD1 expression and the abundance of CD8+ T cells. Functional enrichment analyses revealed that immune response and cytokine-cytokine receptor are very critical signaling pathways which associated with MITD1 in KIRC. In conclusion, our findings indicated that MITD1 may be a potential biomarker and associated with immune infiltration in KIRC.

scholarly journals The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3963
Author(s):  
Brendah K. Masisi ◽  
Rokaya El Ansari ◽  
Lutfi Alfarsi ◽  
Madeleine L. Craze ◽  
Natasha Jewa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Glutamine Metabolism ◽  
Gene Copy ◽  
Luminal Breast Cancer ◽  
Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

scholarly journals HOTAIR as a Prognostic Predictor for Diverse Human Cancers: A Meta- and Bioinformatics Analysis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 778 ◽  
Author(s):  
Halil Ibrahim Toy ◽  
Didem Okmen ◽  
Panagiota I. Kontou ◽  
Alexandros G. Georgakilas ◽  
Athanasia Pavlopoulou
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Human Cancers ◽  
Potential Biomarker

Several studies suggest that upregulated expression of the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is a negative predictive biomarker for numerous cancers. Herein, we performed a meta-analysis to further investigate the prognostic value of HOTAIR expression in diverse human cancers. To this end, a systematic literature review was conducted in order to select scientific studies relevant to the association between HOTAIR expression and clinical outcomes, including overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS)/metastasis-free survival (MFS) of cancer patients. Collectively, 53 eligible studies including a total of 4873 patients were enrolled in the current meta-analysis. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between HOTAIR and cancer patients’ survival. Elevated HOTAIR expression was found to be significantly associated with OS, RFS/DFS and PFS/MFS in diverse types of cancers. These findings were also corroborated by the results of bioinformatics analysis on overall survival. Therefore, based on our findings, HOTAIR could serve as a potential biomarker for the prediction of cancer patient survival in many different types of human cancers.

scholarly journals Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo

Oncogene ◽  
2000 ◽  
Vol 19 (4) ◽  
pp. 505-513 ◽  
Author(s):  
V A Krutovskikh ◽  
S M Troyanovsky ◽  
C Piccoli ◽  
H Tsuda ◽  
M Asamoto ◽  
...  
Keyword(s):  
Cell Growth ◽  
Subcellular Localization ◽  
Tumor Cell ◽  
Gap Junction ◽  
Differential Effect ◽  
Tumor Cell Growth ◽  
Junction Protein ◽  
Gap Junction Protein

scholarly journals MiR-140-5p suppresses retinoblastoma cell growth via inhibiting c-Met/AKT/mTOR pathway

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Yujun Liao ◽  
Xiaolong Yin ◽  
Yan Deng ◽  
Xiaowei Peng
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Large Set ◽  
Retinoblastoma Cell ◽  
Cycle Arrest ◽  
Potential Biomarker ◽  
N Classification ◽  
Mirnas Expression ◽  
T Classification

MiR-140-5p is low expression and acts as a tumor suppressor in various types of human cancers. However, the potential role of miR-140-5p in retinoblastoma (RB) remains unknown. In the present study, we performed the miRNA microarray analysis to investigate whether miRNAs expression are associated with RB tumorigenesis in RB tissues. We found that a large set of miRNAs were ectopic expressions and miR-140-5p is most significantly down-regulated in human RB tissues compared with normal retinas. In addition, low miR-140-5p expression is associated with clinicopathological features (differentiation, invasion, T classification, N classification, cTNM stage, and largest tumor base) and poor survival in RB patients. Furthermore, our results showed that overexpression of miR-140-5p suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell. Meanwhile, we confirmed that c-Met is the functional target of miR-140-5p in RB cell, and miR-140-5p expression is negatively correlated with c-Met in RB tissues. We also found that inhibition of c-Met also suppresses proliferation and induces apoptosis and cell cycle arrest in RB cell. Interestingly, c-Met can rescue the suppressive effects of miR-140-5p on RB cell growth and cell cycle arrest. More importantly, our findings indicated that miR-140-5p may inhibit cell growth via blocking c-Met/AKT/mTOR signaling pathway. Collectively, these results suggested that miR-140-5p might be a potential biomarker and target in the diagnosis and treatment of RB.

243 PROGNOSTIC IMPACT OF CXCR7 AND CXCL12 EXPRESSION IN PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Masakazu Goto ◽  
Yukiko Shibahara ◽  
Cristina Baciu ◽  
Frances Allison ◽  
Mathieu Derouet ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
High Expression ◽  
Average Score ◽  
Prognostic Impact ◽  
Cell Trafficking ◽  
Multiple Cancer ◽  
Cxcl12 Expression ◽  
Potential Biomarker

Abstract   Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have recently been reported as biomarkers in various cancers, including esophageal squamous cell carcinoma; however, there are few studies of these chemokines in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4 and CXCR7, and prognosis in patients with EAC. Methods This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4 and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and scored based on a semiquantitative scoring system. The average score from multiple cancer tissues on the microarray was utilized and patients were divided into high or low expression groups using the median score as a cutoff point. These results were compared with the patients’ clinicopathological features and survival. Results The score of CXCR7 was positively correlated with that of CXCL12 (r = 0.3154). High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005), higher number of lymph node metastases (pN0–1 vs pN2–3, P = 0.0014) and TNM stage (Stage I-II vs III-IV, P = 0.0168). Patients with high CXCR7 (n = 23) expression was associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for DFS on multivariable analysis (HR0.3, 95%CI: 0.1–0.8, P = 0.0115). Conclusion High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 and its ligand CXCL12, had a stronger association on prognosis. Further study of this potential biomarker using whole tissue samples and larger sample size is warranted.

scholarly journals An Alternatively Translated Connexin 43 Isoform, GJA1-11k, Localizes to the Nucleus and Can Inhibit Cell Cycle Progression

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 473
Author(s):  
Irina Epifantseva ◽  
Shaohua Xiao ◽  
Rachel E. Baum ◽  
André G. Kléber ◽  
TingTing Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Gap Junction ◽  
Connexin 43 ◽  
Cell Cycle Progression ◽  
Tumor Formation ◽  
Full Length ◽  
Cycle Progression ◽  
Junction Protein ◽  
Truncated Isoforms

Connexin 43 (Cx43) is a gap junction protein that assembles at the cell border to form intercellular gap junction (GJ) channels which allow for cell–cell communication by facilitating the rapid transmission of ions and other small molecules between adjacent cells. Non-canonical roles of Cx43, and specifically its C-terminal domain, have been identified in the regulation of Cx43 trafficking, mitochondrial preconditioning, cell proliferation, and tumor formation, yet the mechanisms are still being explored. It was recently identified that up to six truncated isoforms of Cx43 are endogenously produced via alternative translation from internal start codons in addition to full length Cx43, all from the same mRNA produced by the gene GJA1. GJA1-11k, the 11kDa alternatively translated isoform of Cx43, does not have a known role in the formation of gap junction channels, and little is known about its function. Here, we report that over expressed GJA1-11k, unlike the other five truncated isoforms, preferentially localizes to the nucleus in HEK293FT cells and suppresses cell growth by limiting cell cycle progression from the G0/G1 phase to the S phase. Furthermore, these functions are independent of the channel-forming full-length Cx43 isoform. Understanding the apparently unique role of GJA1-11k and its generation in cell cycle regulation may uncover a new target for affecting cell growth in multiple disease models.

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