The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

Ernst, Simone; Heinzelmann, Joana; Bohle, Rainer M.; Weber, Georg F.; Stöckle, Michael; Junker, Kerstin; Heinzelbecker, Julia

doi:10.1111/andr.12838

Cited by 14 publications

(5 citation statements)

References 30 publications

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“…Knowledge of microRNA hsa-miR-758-5p and its role in cancer progression are limited. This miRNA was differentially expressed in metastatic compared with non-metastatic seminomatous germ cell tumors ( 32 ). However, the mechanistic connection between expression of this microRNA and aGCT recurrence is still unclear.…”

Section: Resultsmentioning

confidence: 99%

Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Khlebus

Vuttaradhi

Welte

et al. 2023

Molecular Cancer Research

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Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary and recurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using “clusterProfiler” and “GSVA” R packages. TME composition was investigated through the analysis and integration of multiple published RNA-seq deconvolution algorithms. TME analysis results were externally validated using data from independent previously published RNA-seq datasets. A total of 31 DEGs were identified between primary and recurrent aGCTs. These included genes with known function in hormone signaling such as LHCGR and INSL3 (more abundant in primary tumors) and CYP19A1 (more abundant in recurrent tumors). Gene set enrichment analysis revealed that primarily immune-related and hormone-regulated gene sets expression was increased in recurrent tumors. Integrative TME analysis demonstrated statistically significant depletion of cancer-associated fibroblasts in recurrent tumors. This finding was confirmed in multiple independent datasets. Implications: Recurrent aGCTs exhibit alterations in hormone pathway gene expression as well as decreased infiltration of cancer-associated fibroblasts, suggesting dual roles for hormonal signaling and TME remodeling underpinning disease relapse.

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Section: Resultsmentioning

confidence: 99%

Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Khlebus

Vuttaradhi

Welte

et al. 2023

Molecular Cancer Research

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“…There are few studies on hsa-miR-371a-5p, and they are mainly focused on tumors and inflammation-related studies. Ernst et al's research showed that the miRNA microarray results changed significantly in term and preterm placentas, among which hsa-miR-371a-5p showed significant changes (32). However, Jang et al used RT-qPCR to verify the samples (both term and preterm placentas) in large quantities and found that hsa-miR-371a-5p did not change significantly, while hsa-miR-371a-5p was confirmed to be able to regulate the inflammatory target gene LEF1 found in the samples (33).…”

Section: Discussionmentioning

confidence: 99%

Possible causes of atherosclerosis: lncRNA COLCA1 induces oxidative stress in human coronary artery endothelial cells and impairs wound healing

Li¹,

Hao²,

Yan³

et al. 2022

Ann Transl Med

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Background: Atherosclerosis is the most common cause of cardiovascular disease, accompanied by high mortality and poor prognosis. Low-density lipoprotein (LDL) and its oxidized form oxidized low-density lipoprotein (oxLDL) play an important role in atherosclerosis. This article will explore the role of the lncRNA COLCA1 (colorectal cancer associated 1)/hsa-miR-371a-5p/SPP1 (secreted phosphoprotein 1) pathway in oxLDL in causing human coronary artery endothelial cells (HCAECs) inflammation and related biological function changes.Methods: OxLDL was used to stimulate HCAECs. The inflammatory response and biological function changes of HCAECs were analyzed, total RNA-seq was performed on HCAECs before and after stimulation, and RT-Qpcr (real-time quantitative PCR) was used to verify the differential genes. Interference of the expression of COLCA1 in HCAECs was performed by siRNA interference technology to verify the role of COLCA1 in the biological function changes of HCAECs after oxLDL stimulation, and further prove that COLCA1 affects SPP1 through hsa-miR-371a-5p.Results: OxLDL can affect the oxidative stress response of HCAECs, which in turn affects the apoptosis and wound healing ability of HCAECs. COLCA1 and SPP1 were highly expressed after oxLDL stimulation, while hsa-miR-371a-5p was the opposite. After COLCA1 interference, the oxidative stress level of HCAECs stimulated by oxLDL decreased, the apoptosis level also significantly decreased, and the wound healing ability was enhanced. After simultaneous COLCA1 interference and recovery of the expression of hsa-miR-371a-5p, these improved functions disappeared. The dual-luciferase assay confirmed that hsa-miR-371a-5p and COLCA1, hsa-miR-371a-5p and SPP1 has binding targets.Conclusions: OxLDL can up-regulate the expression of COLCA1 in HCAECs, which in turn affects the intracellular COLCA1/hsa-miR-371a-5p/SPP1 pathway to regulate the level of oxidative stress in cells. This in turn affects the level of apoptosis and wound healing ability, which causes cells to produce a continuous inflammatory response.

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“…Based on these results, miR-371a-3p may have limited utility as a tool for risk stratification. There are, however, some other members of miRNA family such as miR-29c-5p, miR-506-3p, miR-1307-5p, and miR-371a-5p that have shown potential capability to act as a prognostic marker in SGCT [ 44 ]. The results of currently recruiting trials, where prospective and serial collection of miRNAs are performed at different stages, will provide more definitive evidence in this regard.…”

Section: Prognostic Markermentioning

confidence: 99%

MicroRNA-371a-3p as a blood-based biomarker in testis cancer

Ahmadi

Jang

Daneshmand

et al. 2021

Asian Journal of Urology

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MicroRNAs (miRNAs) are small noncoding RNAs involved in the regulation of mRNA transcription and translation, and possess all desirable features of an ideal tumor marker. Of almost 31 different miRNA clusters identified in germ cell tumors (GCTs), miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous GCTs. It is easily obtainable and correlates well with tumor burden. Recent multi-institutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%–100% sensitivity and 90%–100% specificity. This accuracy may address other unmet needs in the management of patients with GCT. Early studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II disease. Ongoing clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I GCT. Despite its strong association with viable GCT after treatment with chemotherapy, miR-371a-3p does not seem to accurately predict the presence of teratoma in residual lesions. Also, standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.

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The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

Cited by 14 publications

References 30 publications

Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors

Possible causes of atherosclerosis: lncRNA COLCA1 induces oxidative stress in human coronary artery endothelial cells and impairs wound healing

MicroRNA-371a-3p as a blood-based biomarker in testis cancer

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