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2022 ◽  
Author(s):  
Leming Shi ◽  
Jun Shang ◽  
Yue Zhao ◽  
He Jiang ◽  
Jingcheng Yang ◽  
...  

Abstract Patients with adenocarcinomas in situ (AIS) and minimally invasive (MIA) lung adenocarcinoma (LUAD) are curable by surgery, whereas 20% stage I patients die within five years post-operative. We hypothesize that poor-prognosis stage I patients may exhibit key molecular characteristics deviating from AIS/MIA. Focal adhesion (FA) was identified as the only pathway significantly perturbed at both genomic and transcriptomic levels by comparing 98 AIS/MIA and 99 LUAD. Then, two FA genes (COL11A1 and THBS2) were found strongly upregulated from AIS/MIA to stage I while steadily expressed from normal to AIS/MIA. Furthermore, unsupervised clustering separated stage I patients into two molecularly and prognostically distinct subtypes (S1 and S2) based on COL11A1 and THBS2 expressions (FA2). Subtype S1 resembled AIS/MIA, whereas S2 exhibited more somatic alterations and activated cancer-associated fibroblast. The simple knowledge-driven model was validated with 12 external datasets, showing potential in identifying high-risk stage I patients for more intensive post-surgery treatment.


Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 122
Author(s):  
Natpaphan Yawut ◽  
Il-Rae Cho ◽  
Phatcharaporn Budluang ◽  
Sirichat Kaowinn ◽  
Chutima Kaewpiboon ◽  
...  

Overexpression of cancer upregulated gene (CUG) 2 induces cancer stem cell-like phenotypes, such as enhanced epithelial-mesenchymal transition, sphere formation, and doxorubicin resistance. However, the precise mechanism of CUG2-induced oncogenesis remains unknown. We evaluated the effects of overexpression of CUG2 on microRNA levels using a microRNA microarray. Levels of miR-3656 were decreased when CUG2 was overexpressed; on the basis of this result, we further examined the target proteins of this microRNA. We focused on Jumonji C domain-containing protein 5 (JMJD5), as it has not been previously reported to be targeted by miR-3656. When CUG2 was overexpressed, JMJD5 expression was upregulated compared to that in control cells. A 3′ untranslated region (UTR) assay revealed that an miR-3656 mimic targeted the JMJD5 3′UTR, but the miR-3656 mimic failed to target a mutant JMJD5 3′UTR, indicating that miR-3656 targets the JMJD5 transcript. Administration of the miR-3656 mimic decreased the protein levels of JMD5 according to Western blotting. Additionally, the miR-3656 mimic decreased CUG2-induced cell migration, evasion, and sphere formation and sensitized the cells to doxorubicin. Suppression of JMJD5, with its small interfering RNA, impeded CUG2-induced cancer stem cell-like phenotypes. Thus, overexpression of CUG2 decreases miR-3656 levels, leading to upregulation of JMJD5, eventually contributing to cancer stem cell-like phenotypes.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Elham Kalantari ◽  
Tahereh Taheri ◽  
Saba Fata ◽  
Maryam Abolhasani ◽  
Mitra Mehrazma ◽  
...  

Abstract Background The crucial oncogenic role of cancer stem cells (CSCs) in tumor maintenance, progression, drug resistance, and relapse has been clarified in different cancers, particularly in colorectal cancer (CRC). The current study was conducted to evaluate the co-expression pattern and clinical significance of epithelial cell adhesion molecules (EpCAM) and activated leukocyte cell adhesion (CD166 or ALCAM) in CRC patients. Methods This study was carried out on 458 paraffin-embedded CRC specimens by immunohistochemistry on tissue microarray (TMA) slides. Results Elevated expression of EpCAM and CD166 was observed in 61.5% (246/427) and 40.5% (164/405) of CRC cases. Our analysis showed a significant positive association of EpCAM expression with tumor size (P = 0.02), tumor stage (P = 0.007), tumor differentiate (P = 0.005), vascular (P = 0.01), neural (P = 0.01), and lymph node (P = 0.001) invasion. There were no significant differences between CD166 expression and clinicopathological parameters. Moreover, the combined analysis demonstrated a reciprocal significant correlation between EpCAM and CD166 expression (P = 0.02). Interestingly, there was a significant positive correlation between EpCAM/CD166 phenotypes expression and tumor stage (P = 0.03), tumor differentiation (P = 0.05), neural, and lymph node invasion (P =0.01). Conclusions The significant correlation of EpCAM and CD166 expression and their association with tumor progression and aggressive behavior is the reason for the suggestion of these two CSC markers as promising targets to promote novel effective targeted-therapy strategies for cancer treatment in the present study.


Author(s):  
Xavier León ◽  
Jacinto García ◽  
Albert Pujol ◽  
Julia de Juan ◽  
Rosselin Vásquez ◽  
...  

Abstract Purpose Proviral integration site for Moloney murine leukemia virus (PIMs) are proto-oncogenes encoding serine/threonine kinases that phosphorylate a variety of substrates involved in the regulation of cellular processes. Elevated expression of PIM-1 has been associated with poor prognosis in several types of cancer. There are no studies that have analyzed the response to radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) according to the expression of PIM-1. The aim of our study was to analyze the relationship between the transcriptional expression of PIM-1 and local response to radiotherapy in HNSCC patients. Methods We determined the transcriptional expression of PIM-1 in 135 HNSCC patients treated with radiotherapy, including patients treated with chemoradiotherapy (n = 65) and bioradiotherapy (n = 15). Results During the follow-up, 48 patients (35.6%) had a local recurrence of the tumor. Patients with local recurrence had a higher level of PIM-1 expression than those who achieved local control of the disease (P = 0.017). Five-year local recurrence-free survival for patients with a high expression of PIM-1 (n = 43) was 44.6% (95% CI 29.2–60.0%), and for patients with low expression (n = 92) it was 71.9% (95% CI 62.5–81.3%) (P = 0.007). According to the results of multivariate analysis, patients with a high PIM-1 expression had a 2.2-fold increased risk of local recurrence (95% CI 1.22–4.10, P = 0.009). Conclusion Patients with elevated transcriptional expression levels of PIM-1 had a significantly higher risk of local recurrence after radiotherapy.


2022 ◽  
Author(s):  
Quan-Bing Zhang ◽  
A-Ying Liu ◽  
Qiao-Zhou Fang ◽  
Hai-Yang Zhang ◽  
Feng Wang ◽  
...  

Abstract Background: The aim of this study was to investigate the therapeutic effect of electrical stimulation on disuse muscular atrophy in a rabbit model of knee joint contracture and explore the role of endoplasmic reticulum stress-induced Parkin-dependent mitophagy in this process.Methods: Two sub-experiments were carried out successively in our study. In the first sub-experiment, 24 rabbits were divided into four groups on average based on the immobilization time: Ctrl 1, I-2, I-4, and I-6 groups. In the second sub-experiment, 24 rabbits were also divided into four groups on average in accordance with the process mode: Ctrl2, ES, NR, and EST groups. To test the time-dependent changes of the rectus femoris muscles after immobilization in rabbits, and to evaluate the effect of electrical stimulation on the atrophic rectus femoris muscles, the wet weights of rectus femoris muscles were assessed in this study, along with the protein levels of atrogin-1, p-PERK, Parkin and COXIV.Results: The wet weights of rectus femoris muscles, the protein levels of atrogin-1, p-PERK and Parkin increased after immobilization. It was also revealed that the protein levels of COXIV decreased after immobilization. Electrical stimulation was effective against muscle atrophy, the elevated expression of atrogin-1, p-PERK, Parkin, and the decreased expression of COXIV.Conclusions: Immobilization of unilateral lower limb could induce rectus femoris muscle atrophy, endoplasmic reticulum stress and Parkin mediated mitophagy. Endoplasmic reticulum stress-induced Parkin-dependent mitophagy may be one of the mechanisms by which electrical stimulation can play a significant role.


2022 ◽  
Vol 8 ◽  
Author(s):  
Ying Jiang ◽  
Hong Zhu ◽  
Hong Chen ◽  
Yi-Chen Yu ◽  
Ye-Tao Xu ◽  
...  

Cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, the potential molecular mechanisms for such long-term outcomes are still unknown. Here, we found that systolic blood pressure was a little higher in IVF born offspring at 2 years old compared to those born after being naturally conceived. Besides, the expression level of maternally expressed gene 3 (MEG3) was higher in human umbilical vein endothelial cells (HUVECs) from IVF offspring than that in spontaneously born offspring. Pearson correlation test showed that MEG3 relative expression is significantly related to the children's blood pressure (Coefficient = 0.429, P = 0.0262). Furthermore, we found decreased expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) along with elevated expression of endothelial-1(ET1) in HUVECs from IVF offspring, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1 in the umbilical cord serum of IVF offspring. Correlation analysis showed MEG3 expression highly correlated with ET1 and Nitrate concentration. With pyrosequencing technology, we found that elevated expression of MEG3 was the result of hypomethylation of the MEG3 promoter. Therefore, our results provide a potential mechanism addressing the high-risk of hypertension in IVF offspring via MEG3 epigenetic regulation.


2022 ◽  
Vol 163 (1) ◽  
pp. 3-11

Összefoglaló. A malignus daganat és a stroke egy-egy betegnél gyakran kombinálódik, sokszor egyidejűleg diagnosztizálják, vagy rövid idő telik el a két kórkép felismerése között. Az együttes megjelenés hátterében elsősorban a hasonló tradicionális rizikófaktorok állhatnak: az idősebb életkor, a magas vérnyomás, a hyperlipidaemia, a cukorbetegség, az elhízás és a dohányzás. Az átfedő kockázati tényezőkön túl a daganat által okozott hiperkoaguláció artériás és vénás thrombosis kialakulásához vezethet. A hiperkoaguláció hátterének kutatása főként a thrombocyták és a szöveti faktor aktiválására és a heparanáz fokozott expressziójára fókuszált, és felvetődött a neutrophil extracelluláris csapdák szerepe is. A daganat által okozott hiperkoagulációhoz társuló cryptogen (tradicionális rizikófaktor nélküli) stroke-ban sokszor található magasabb D-dimer-szint, és a CT/MRI-képeken gyakrabban látszanak multifokális, több ér ellátási területében megjelenő ischaemiás laesiók, melyek ritkábban fordulnak elő a tradicionális rizikófaktorokkal magyarázható stroke-okban. Az előzőkön kívül a daganatok kezelésére alkalmazott kemoterápia és sugárterápia is emeli a stroke kockázatát. A malignus daganatokhoz társuló stroke-ok megelőzése érdekében további vizsgálatok szükségesek a daganat által okozott hiperkoaguláció és vascularis változások pontosabb megértéséhez. Orv Hetil. 2022; 163(1): 3–11. Summary. Cancer and stroke have long been studied individually, but their detrimental forces together have also been a strong point of focus. The occurrence of both cancer and stroke in a patient is often a reflection of their similar risk factors (hypertension, hyperlipidemia, diabetes, obesity, and smoking), however, a subgroup of the cancer stroke population is believed to occur due to cancer-associated hypercoagulability. A deeper look into the cancer-associated hypercoagulable environment has indicated that thrombosis may be explained by cancer’s role in several factors, including activation of platelets and tissue factor, elevated expression of heparanase and influence on neutrophilic extracellular traps. When a cryptogenic stroke (stroke lacking the aforementioned risk factors) occurs due to the cancer-induced hypercoagulation state, patient serum D-dimer levels have been found elevated, and CT/MRI images of the brain have shown multivascular infarctions compared to stroke patients with traditional risk factors. Additionally, cancer treatment – chemotherapy and radiation – have also been found to increase the occurrence of cerebral vascular thrombosis. Further investigations are required to better understand cancer-associated vascular pathophysiologic changes and how to discern their unique strokes compared to strokes from other etiologies. With these insights, the prevalence of strokes in the cancer population could be decreased. Orv Hetil. 2022; 163(1): 3–11.


OCL ◽  
2022 ◽  
Vol 29 ◽  
pp. 3
Author(s):  
Mohammad Mahdi Taghvaei ◽  
Habibollah Samizadeh Lahiji ◽  
Mohammad Mohsenzadeh Golfazani

Rapeseed is the third-largest source of plant oil and one of the essential oil plants worldwide. Cold stress is one of the critical factors that affect plant yield. Therefore, improving cold stress tolerance is necessary for yield increase. The present study investigated BnCAT1 and BnCSD1 genes’ expression behavior in a tolerant and sensitive cultivar under cold stress (4 °C). Besides, protein-protein interaction networks of CATs and CSDs enzymes, and their association with other antioxidant enzymes were analyzed. Moreover, the microRNAs targeting BnCAT1 and BnCSD1 genes were predicted. This study indicated many direct and indirect interactions and the association between the components of the plant antioxidant system. However, not only did the CATs and CSDs enzymes have a relationship with each other, but they also interacted directly with ascorbate peroxidase and glutathione reductase enzymes. Also, 23 and 35 effective microRNAs were predicted for BnCAT1 and BnCSD1 genes, respectively. The gene expression results indicated an elevated expression of BnCAT1 and BnCSD1 in both tolerant and sensitive cultivars. However, this increase was more noticeable in the tolerant cultivar. Thus, the BnCSD1 gene had the highest expression in the early hour of cold stress, especially in the 12th h, and the BnCAT1 gene showed the highest expression in the 48th h. This result may indicate a functional relationship between these enzymes.


2021 ◽  
Vol 8 (12) ◽  
pp. 4782-4792
Author(s):  
Tien-Manh Hoang ◽  
Minh-Tien Nguyen ◽  
Weisin Chen ◽  
Chenyang Zhuang ◽  
Zixiang Wang ◽  
...  

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