Emerging Roles of Long Non-coding RNAs in Uterine Leiomyoma Pathogenesis: a Review

Falahati, Zahra; Mohseni-Dargah, Masoud; Mirfakhraie, Reza

doi:10.1007/s43032-021-00571-w

Cited by 9 publications

(10 citation statements)

References 130 publications

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“…Significant alteration in the synthesis profile of regulatory microRNAs of the families let7, miR-21, miR-93, miR-106b, miR-29, and miR-200 has been observed ( 334 , 335 ). More recently, studies on the role of long non-coding RNAs in the pathogenesis of uterine fibroids have been investigated, further demonstrating the critical role of RNA network in uterine fibroids ( 332 , 336-338 ). Epigenetic changes in the uterine fibroid genome can activate critical transduction signaling pathways, such as Wnt/β-catenin and Wnt/MAPK ( 320 , 339 ).…”

Section: Key Pathways Contributing To Uterine Fibroids Formationmentioning

confidence: 99%

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

et al. 2021

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Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or non-invasive treatment option exists for hormone-dependent uterine fibroids due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on their risk factors, development origin, pathogenetic mechanisms, and treatment options. Additionally, we describe the current treatment interventions for uterine fibroids. Finally, future perspectives on uterine fibroids studies are summarized. Deeper mechanistic insights into tumor etiology and uterine fibroids’ complexity can contribute to the newer targeted therapies.

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Section: Key Pathways Contributing To Uterine Fibroids Formationmentioning

confidence: 99%

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

et al. 2021

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“…There are higher prevalence and symptom severity in African Americans [ 5 ] compared with Caucasian women. The mechanisms underlying the pathogenesis of leiomyomas have been under intense investigation and recent evidence using microarrays and next-generation RNA sequencing has indicated aberrant expression of a host of protein-coding genes and non-coding RNA (ncRNA) in leiomyomas, including long and small non-coding RNA (lncRNA and sncRNA), which play crucial roles in regulation of protein-coding genes through post-transcriptional, transcriptional, and epigenetic mechanisms [ 6 , 7 , 8 , 9 , 10 , 11 ]. These tumors are also characterized by genetic heterogeneity with chromosomal re-arrangements, and mutations in a number of driver genes such as MED12 (mediator complex subunit 12), FH (fumarate hydratase), HMGA2 (high mobility group AT-hook 2), and COL4A5/6 (collagen type IV alpha 5 and alpha 6).…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas

Chuang

Gao²,

Quintanilla³

et al. 2023

IJMS

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Recent studies have demonstrated that somatic MED12 mutations in exon 2 occur at a frequency of up to 80% and have a functional role in leiomyoma pathogenesis. The objective of this study was to elucidate the expression profile of coding RNA transcripts in leiomyomas, with and without these mutations, and their paired myometrium. Next-generation RNA sequencing (NGS) was used to systematically profile the differentially expressed RNA transcripts from paired leiomyomas (n = 19). The differential analysis indicated there are 394 genes differentially and aberrantly expressed only in the mutated tumors. These genes were predominantly involved in the regulation of extracellular constituents. Of the differentially expressed genes that overlapped in the two comparison groups, the magnitude of change in gene expression was greater for many genes in tumors bearing MED12 mutations. Although the myometrium did not express MED12 mutations, there were marked differences in the transcriptome landscape of the myometrium from mutated and non-mutated specimens, with genes regulating the response to oxygen-containing compounds being most altered. In conclusion, MED12 mutations have profound effects on the expression of genes pivotal to leiomyoma pathogenesis in the tumor and the myometrium which could alter tumor characteristics and growth potential.

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“…Therefore, it is urgent to find new etiological and pathological features of UL to improve the diagnostic efficiency of UL ( Yuan et al, 2021 ). To date, little is known about the pathogenesis of UL, leading to the lack of a valid medical treatment ( Falahati et al, 2021 ). However, there is considerable evidence that estrogen plays a major role in the proliferation of these benign tumors ( Ulin et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, there is considerable evidence that estrogen plays a major role in the proliferation of these benign tumors ( Ulin et al, 2020 ). While a strong correlation between ovarian hormone levels or age and the development of UL was found, recent studies of UL have identified novel genes or pathways suggesting the differential expression of mRNAs and lncRNA of this disease progression in order to improve the early detection of tumor and early intervention and treatment of UL ( Nothnick, 2016 ; Falahati et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

An integrative analysis of an lncRNA–mRNA competing endogenous RNA network to identify functional lncRNAs in uterine leiomyomas with RNA sequencing

Meng

Chen

et al. 2023

Front. Genet.

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Objective: To explore the functions of mRNAs and lncRNAs in the occurrence of uterine leiomyomas (ULs) and further clarify the pathogenesis of UL by detecting the differential expression of mRNAs and lncRNAs in 10 cases of UL tissues and surrounding normal myometrial tissues by high-throughput RNA sequencing.Methods: The tissue samples of 10 patients who underwent hysterectomy for UL in Lianyungang Maternal and Child Health Hospital from January 2016 to December 2021 were collected. The differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified and further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein–protein interaction network (PPI) was constructed in Cytoscape software. Functional annotation of the nearby target cis‐DEmRNAs of DElncRNAs was performed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) (https://david.ncifcrf.gov/). Meanwhile, the co-expression network of DElncRNA–DEmRNA was constructed in Cytoscape software.Results: A total of 553 DElncRNAs (283 upregulated DElncRNAs and 270 downregulated DElncRNAs) and 3,293 DEmRNAs (1,632 upregulated DEmRNAs and 1,661 downregulated DEmRNAs) were obtained. GO pathway enrichment analysis revealed that several important pathways were significantly enriched in UL such as blood vessel development, regulation of ion transport, and external encapsulating structure organization. In addition, cytokine–cytokine receptor interaction, neuroactive ligand–receptor interaction, and complement and coagulation cascades were significantly enriched in KEGG pathway enrichment analysis. A total of 409 DElncRNAs–nearby-targeted DEmRNA pairs were detected, which included 118 DElncRNAs and 136 DEmRNAs. Finally, we found that the top two DElncRNAs with the most nearby DEmRNAs were BISPR and AC012531.1.Conclusion: These results suggested that 3,293 DEmRNAs and 553 DElncRNAs were differentially expressed in UL tissue and normal myometrium tissue, which might be candidate-identified therapeutic and prognostic targets for UL and be considered as offering several possible mechanisms and pathogenesis of UL in the future.

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Emerging Roles of Long Non-coding RNAs in Uterine Leiomyoma Pathogenesis: a Review

Cited by 9 publications

References 130 publications

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas

An integrative analysis of an lncRNA–mRNA competing endogenous RNA network to identify functional lncRNAs in uterine leiomyomas with RNA sequencing

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