Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer

xlomafota13 shared this article with you from Inoreader Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5402-5414. eCollection 2021. ABSTRACT m6A methylation has been demonstrated to be one of the most important epigenetic regulation mechanisms in cell differentiation and cancer development especially m6A derived diagnostic and prognostic biomarkers have been identified in the past several years. However, systemic investigation to the interaction between germline single-nucleotide polymorphisms (SNPs) and m6A has not been conducted yet. In this study, we collected previous identified significant thyroid cancer associated SNPs from UKB cohort (358 cases and 407,399 controls) and ICR cohort (3,001 patients and 287,550 controls) and thyroid eQTL (sample size = 574 from GTEx project) and m6A-SNP (N = 1,678,126) were applied to prioritize the candidate SNPs. Finally, five candidate genes (PLEKHA8, SMUG1, CDC123, RMI2, ACSM5) were identified to be thyroid cancer associated m6A-related genetic suscepti bility. Loss and gain function studies of m6A writer proteins confirm that ACSM5 is regulated by m6A methylation of mRNA. Moreover, ACSM5 is downregulated in thyroid cancer and inversely correlated with PTC malignancy and patient survival. Together, our study highlight mRNA-seq and m6A-seq double analysis provided a novel approach to identify cancer biomarkers and understanding the heterogeneity of human cancers. PMID:34873468 | PMC:PMC8640822 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

New insights into the functions of progesterone receptor (PR) isoforms and progesterone signaling

xlomafota13 shared this article with you from Inoreader New insights into the functions of progesterone receptor (PR) isoforms and progesterone signaling Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5214-5232. eCollection 2021. ABSTRACT Progesterone, the ovarian steroid hormone, regulates a plentitude of biological processes in tissues ranging from the brain to bones. Recognizing the role of progesterone and its receptors in physiological processes and maladies can prevent and treat various diseases. Apart from its physiological functions, its role in developing diseases, especially breast cancer, is a recent topic of deliberation. There exists conflicting experimental and epidemiological evidence linking progesterone to breast cancer. This review tries to describe the physiological functions of progesterone and its receptors, genomic and non-genomic signaling, splice variants, and a different aspect of progesterone signaling. Furthermore, we seek to address or attempt to discuss the following pertinent questions on steroid hormone signaling; How does progesterone influence breast cancer progres sion? How does it change the molecular pathways in breast cancer with different receptor statuses, the specific role of each isoform, and how does the ER/and PR ratio affect progesterone signaling? PMID:34873457 | PMC:PMC8640821 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment

xlomafota13 shared this article with you from Inoreader DNA methylation markers in esophageal cancer: an emerging tool for cancer surveillance and treatment Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5644-5658. eCollection 2021. ABSTRACT Esophageal carcinoma (EC) is one of the most pervasive cancers in the world, with upwards of 500,000 new diagnoses, annually. Despite its prominence, advancements in the detection and treatment of EC have been marginal over the past 30 years and the survival rate continues to stay below 20%. This is due to the uncommonly heterogeneous presentation of EC which presents unprecedented challenges in improving patient survival and quality of care. However, distinct epigenetic alterations to the DNA methylome may provide an avenue to drastically improve the detection and treatment of EC. Specifically, the creation of novel biomarker panels that consist of EC-specific methylation markers have shown promise as a potential alternative to the more invasive, contemporary diagnostic methods. Additionally, growing insight into the biological and clinical properties of EC-spec ific methylation patterns have opened a window of opportunity for enhanced treatment; of growing interest is the application of "DNMT inhibitors" - a class of drugs which inhibit excessive methylation and have been shown to re-sensitize chemoresistant tumors. Here we provide a comprehensive review of the current advancements in EC DNA methylation to underscore a potential approach to its detection and treatment. PMID:34873485 | PMC:PMC8640794 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morphometric analysis of the lumbar vertebrae and intervertebral discs in relation to abdominal aorta: CT-based study

xlomafota13 shared this article with you from Inoreader Morphometric analysis of the lumbar vertebrae and intervertebral discs in relation to abdominal aorta: CT-based study Via radiol anat Surg Radiol Anat. 2021 Dec 7. doi: 10.1007/s00276-021-02865-9. Online ahead of print. ABSTRACT PURPOSE: Although lumbar discectomy is the most common procedure in spine surgery, reports about anatomical relations between discs and prevertebral vessels are limited. Aim of this research was to investigate morphometric of the lumbar region and the relations between intervertebral discs (IVDs) and abdominal aorta. METHODS: 557 abdominal computed tomography scans were assess ed. For each spinal column level from Th12/L1 down to L4/L5, we investigated: intervertebral disc's and vertebra's height, width, length, and distance from aorta or common iliac artery (CIA). Those arteries were also measured in two dimensions and classified based on location. RESULTS: 54.58% of patients were male. There was a significant difference in arterial-disc distances (ADDs) between genders at the levels: L1/L2 (1.32 ± 1.97 vs. 0.96 ± 1.78 mm; p = 0.0194), L2/L3 (1.97 ± 2.16 vs. 1.15 ± 2.01 mm; p < 0.0001), L3/L4 (2.54 ± 2.78 vs. 1.71 ± 2.61 mm; p = 0.0012), also for both CIAs (left CIA 3.64 ± 3.63 vs. 2.6 ± 3.06 mm; p = 0.0004 and right CIA: 7.96 ± 5.06 vs. 5.8 ± 4.57 mm; p < 0.001)-those ADDs were higher in men at all levels. The length and width of IVD increased alongside with disc level with the maximum at L4/L5. CONCLUSION: Bifurcations of the aorta in most cases occurred at the L4 level. Collected data suggest that at the highest lumbar leve ls, there is a greater possibility to cause injury of the aorta due to its close anatomical relationship with discs. Females have limited, in comparison to males, ADD at L1/L2, L2/L3, and L3/L4 levels what should be taken into consideration during preoperative planning of surgical intervention. PMID:34874459 | DOI:10.1007/s00276-021-02865-9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization

xlomafota13 shared this article with you from Inoreader Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization Via Melanoma Research - Published Ahead-of-Print Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which seru m MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen deprivation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis. * Jaeseob Lee and Young-June Jin contributed equally to the writing of this article. Received 29 March 2021 Accepted 22 September 2021 Correspondence to Hansoo Lee, PhD, Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea, Tel: +82 33 250 8530; e-mail: hslee@kangwon.ac.kr Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.