Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Chehade, Marthe; Bullock, Martyn; Glover, Anthony; Hutvágner, György; Sidhu, Stan

doi:10.3390/cancers12082198

Cited by 15 publications

(12 citation statements)

References 142 publications

(170 reference statements)

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“…Depending on the tissue type, miR-9 can act as a tumor suppressor or as an oncomiR. Similar to previous studies describing many other types of cancer [ 154 ], Yanaihara et al [ 55 ] observed that there is an increased miR-9 expression in OCCC. In addition, luciferase-based assays have demonstrated direct binding between miR-9 and E-cadherin, which is a tumor suppressor protein encoded by the CDH1 gene.…”

Section: A Brief Overview On Mirnas and Their Regulated Targets In Rgcssupporting

confidence: 73%

Could MicroRNAs Be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview

Fiore

Suleiman

Pentimalli

et al. 2021

IJMS

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Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with an annual incidence of <6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience and limited therapeutic options. There has been a growing interest in the field of microRNAs (miRNAs), a class of small non-coding RNAs of ∼22 nucleotides in length, because of their potential to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational repression by interacting with the 3′ untranslated region (3′-UTR) of target mRNAs, as well as other regions and gene promoters, as well as activating translation or regulating transcription under certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few studies have been performed on RGCs. In this review, we summarize the data currently available regarding RGCs.

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Section: A Brief Overview On Mirnas and Their Regulated Targets In Rgcssupporting

confidence: 73%

Could MicroRNAs Be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview

Fiore

Suleiman

Pentimalli

et al. 2021

IJMS

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“…Since CKS2 overexpression has been found to be able to override the DNA damage response barrier triggered by activated oncoproteins [ 40 ], we believe this could be a potential mechanism underlying the correlation between CKS2 and survival of ACC patients. Moreover, through in vitro experiments, Chehade et al found that miR-7, which participates in cell cycle arrest in ACC, acts as a key regulator of CKS2 [ 41 ]. According to these studies, we speculate that miRNAs might play an important role in the regulation of NDRG4 and CKS2, resulting in tumor cell proliferation and aggressiveness, as well as ACC progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis

et al. 2021

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Background Adrenocortical carcinoma (ACC) is an aggressive cancer with heterogeneous outcomes. In this study, we aimed to investigate genomic and prognostic features of ACC. Material/Methods Clinical, pathologic, and transcriptomic data from 2 independent datasets derived from ACC samples (TCGA-ACC dataset, GEO-GSE76021 dataset) were collected. Weighted gene co-expression network analysis (WGCNA) and survival analyses were performed to identify prognostic genes. Pathway analysis was performed for mechanistic analysis. xCell deconvolution was performed for tumor microenvironment analysis. Results In the TCGA-ACC cohort, WGCNA identified a prognostic module of 5408 genes. Differential expression analysis identified 1969 genes that differed in expression level between long-term and short-term survivors. Univariate Cox regression model analysis identified 8393 genes with prognostic value. The intersection of these gene sets included 820 prognostic genes. Similar protocols were performed for the GSE76021 dataset, and 5 candidate genes were identified. Further intersection of these genes finally identified NDRG4 and CKS2 as key prognostic genes. Multivariate Cox regression model analysis validated the prognostic value of NDRG4 (HR=0.61, 95% CI 0.46–0.80) and CKS2 (HR=2.52, 95% CI 1.38–4.60). Moreover, NDRG4 and CKS2 expression predicted survival in patients treated with mitotane ( P <0.001). Further mechanism exploration found an association between CKS2 and DNA mismatch repair pathways. Moreover, NDRG4 positively correlated with CD8 + T cell infiltration, while CKS2 negatively correlated with it. Conclusions We identified NDRG4 and CKS2 expression as key prognostic genes in ACC, which may help in risk stratification of ACC. Moreover, a close relationship was found between CKS2 and mismatch repair pathways. Moreover, immune cell infiltration differed according to NDRG4 and CKS2 expression.

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“…Micro-RNAs (miRNAs) are a class of non-coding, short, singlestranded RNA molecules with the potential to regulate gene output through the translational inhibition of mRNAs. The role of miRNAs in cancer is expanding, and dysregulation of miRNAs currently constitutes a common phenomenon in cancer development, including ACC [196]. For example, specific miRNAs found to be aberrantly expressed include the observed downregulation of miR-195 and upregulation of miR-483-5p-a feature that was also coupled to poorer disease-specific survival [197].…”

Section: Dysregulation Of Micro-rnasmentioning

confidence: 99%

What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics

et al. 2021

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Approximately one-tenth of the general population exhibit adrenal cortical nodules, and the incidence has increased. Afflicted patients display a multifaceted symptomatology-sometimes with rather spectacular features. Given the general infrequency as well as the specific clinical, histological, and molecular considerations characterizing these lesions, adrenal cortical tumors should be investigated by endocrine pathologists in high-volume tertiary centers. Even so, to distinguish specific forms of benign adrenal cortical lesions as well as to pinpoint malignant cases with the highest risk of poor outcome is often challenging using conventional histology alone, and molecular genetics and translational biomarkers are therefore gaining increased attention as a possible discriminator in this context. In general, our understanding of adrenal cortical tumorigenesis has increased tremendously the last decade, not least due to the development of next-generation sequencing techniques. Comprehensive analyses have helped establish the link between benign aldosterone-producing adrenal cortical proliferations and ion channel mutations, as well as mutations in the protein kinase A (PKA) signaling pathway coupled to cortisol-producing adrenal cortical lesions. Moreover, molecular classifications of adrenal cortical tumors have facilitated the distinction of benign from malignant forms, as well as the prognostication of the individual patients with verified adrenal cortical carcinoma, enabling high-resolution diagnostics that is not entirely possible by histology alone. Therefore, combinations of histology, immunohistochemistry, and next-generation multi-omic analyses are all needed in an integrated fashion to properly distinguish malignancy in some cases. Despite significant progress made in the field, current clinical and pathological challenges include the preoperative distinction of non-metastatic low-grade adrenal cortical carcinoma confined to the adrenal gland, adoption of individualized therapeutic algorithms aligned with molecular and histopathologic risk stratification tools, and histological confirmation of functional adrenal cortical disease in the context of multifocal adrenal cortical proliferations. We herein review the histological, genetic, and epigenetic landscapes of benign and malignant adrenal cortical neoplasia from a modern surgical endocrine pathology perspective and highlight key mechanisms of value for diagnostic and prognostic purposes.

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Key MicroRNA’s and Their Targetome in Adrenocortical Cancer

Cited by 15 publications

References 142 publications

Could MicroRNAs Be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview

Could MicroRNAs Be Useful Tools to Improve the Diagnosis and Treatment of Rare Gynecological Cancers? A Brief Overview

Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis

What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics

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