Integrated analysis reveals candidate mRNA and their potential roles in uterine leiomyomas

Xia, Liping; Liu, Yan; Fu, Yan; Dongye, Shengyi; Wang, Dewei

doi:10.1111/jog.13172

Cited by 8 publications

(8 citation statements)

References 40 publications

(79 reference statements)

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“…There have been controversies about the effect of ALDH1A1 on uterine leiomyoma. Zaitseva and coworkers found that αSMAnegative fibroblast-like cells of the connective tissue strongly expressed ALDH1A1 in myometrium when compared with uterine leiomyoma [25], which was consist with the research of Xia and colleagues [26]. ALDH1A1 expression was regulated differently in myometrial and fibroid cells by retinol metabolism pathway which may be important in fibroid pathophysiology [27].…”

Section: Fig 10 Transcriptional Expression Of Hub Genes In 20 Different Types Of Cancer Diseases (Oncomine Database)mentioning

confidence: 53%

Bioinformatic Analysis Identifies potential key genes in the pathogenesis of uterine leiomyoma

2021

European Journal of Gynaecological Oncology

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The present study aimed to screen hub genes for pathology of uterine leiomyoma. Methods: The microarray data of GSE31699, containing 16 uterine leiomyoma tissue samples and 16 matched normal myometrium samples, were downloaded from the Gene Expression Omnibus database (GEO). The "limma" R language package was used to identify di ferently-expressed genes (DEGs) between uterine leiomyoma and myometrium. Gene Ontology (GO) and pathway enrichment analyses were performed by using clusterprofiler, the DEGs were mostly enriched in post-synapse assembly, response to glucocorticoid, extracellular matrix receptor interaction and coagulation cascades. Subsequently, a protein-protein interaction (PPI) network of DEGs was constructed by Search Tool for the Retrieval of Interacting Genes Database (STRING) and visualized by utilizing Cytoscape so tware. We screened hub clusters of PPI network by the plug-in Molecular Complex Detection (MCODE) in Cytoscape, then clusterprofiler was also utilized to analyze functions and pathways enrichment of the genes in the hub clusters. Furthermore, we employed the "WGCNA" package in R to conduct co-expression network for all genes in GSE31699. Ultimately, we selected the overlapped genes in hub clusters of DEGs' PPI network and WGCNA. Results: Five genes (COL5A2, ALDH1A1, GNG11, EFEMP1, ANXA1) were finally validated in other GEO datasets (GSE64763, GSE764, GSE593) and Oncomine database. Gene set enrichment analysis (GSEA) was also performed for the hub genes. The expression of COL5A2 was significantly higher in uterine leiomyoma compared with that in myometrium, while the expression of the other hub genes was significantly lower in uterine leiomyoma. Conclusion: The results indicated that COL5A2, ALDH1A1, GNG11, EFEMP1 and ANXA1 may be the key pathological genes in uterine leiomyoma.

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Section: Fig 10 Transcriptional Expression Of Hub Genes In 20 Different Types Of Cancer Diseases (Oncomine Database)mentioning

confidence: 53%

Bioinformatic Analysis Identifies potential key genes in the pathogenesis of uterine leiomyoma

2021

European Journal of Gynaecological Oncology

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“…Hsa_circ_0056686 is an exon circRNA formed by splicing of the KIF5C mRNA precursor. KIF5C was reported to be involved in the progression of ULM and closely related to ERS [ 15 , 16 ]. The present study showed that hsa_circ_0056686 was upregulated in ULM tissues, which was consistent with those reported by Wang et al suggesting that hsa_circ_0056686 was highly expressed in ULM and was positively related with the leiomyoma size [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0056686, derived from cancer-associated fibroblasts, promotes cell proliferation and suppresses apoptosis in uterine leiomyoma through inhibiting endoplasmic reticulum stress

et al. 2022

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Abnormal expression of circular RNAs (circRNAs) in cancer-associated fibroblasts (CAFs) is involved in the tumor-promoting ability of CAFs. Hsa_ circ_ 0056686 has been reported to affect leiomyoma size. The purpose of this study is to investigate the regulatory role of hsa_circ_0056686 in CAFs on uterine leiomyoma (ULM). The primary CAFs and corresponding normal fibroblasts (NFs) were isolated from the tumor zones of ULM tissues and adjacent, respectively. Hsa_circ_0056686 level was higher in CAFs than NFs, and also higher in ULM tissues than in adjacent tissues. CAFs-CM significantly increased the proliferation and migration and inhibited apoptosis of ULM cells, as confirmed by CCK-8, transwell, and flow cytometry assays. Moreover, conditioned medium (CM) from CAFs transfected with hsa_circ_0056686 shRNA (CAFssh-circ_0056686-CM) abolished CAFs-mediated proliferation, migration and apoptosis of ULM cells. CAFs-CM suppressed the expression of endoplasmic reticulum stress (ERS) marker proteins and induced the expression of extracellular matrix (ECM) marker proteins, thus suppressing ERS and increasing ECM accumulation, which could be declined by CAFssh-circ_0056686-CM. Meanwhile, knockdown of hsa_circ_0056686 reversed the inhibitory effects of CAFs-CM on brefeldin A-induced cell apoptosis. Luciferase gene reporter and RNA pull-down assays indicated that miR-515-5p directly bound with hsa_circ_0056686. MiR-515-5p overexpression restored the hsa_circ_0056686-shRNA-mediated malignant biological behaviors of ULM cells. Hsa_circ_0056686 contributed to tumor-promoting effects of CAFs in ULM, manifested by promoting ULM cell proliferation and migration and reducing ERS-induced apoptosis through sponging miR-515-5p.

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“…Interestingly, recent findings using calpain-6 regulatory sequence–based reporter assays identified calpain-6 as a target gene for a stemness pathway in embryonic stem and cancer cells 33 . Researchers found that calpain-6-expressing cells were tumor-initiating and conferred the property of chemoresistance 37–41 , suggesting an association between calpain-6 and the malignant characteristics of sarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…Calpain-6 was found to be aberrantly expressed in different tumors, and it exhibits both anti-apoptotic and pro-angiogenic functions. Calpain-6 is overexpressed in many types of tumors and induces apoptosis resistance, cell proliferation, and angiogenesis in tumors 37–41 . The association between elevated calpain-6 expression and the inhibition of apoptosis and chemoresistance 37,39,43 suggests its role in the malignant progression of primary tumors.…”

Section: Discussionmentioning

confidence: 99%

Non-proteolytic calpain-6 interacts with VEGFA and promotes angiogenesis by increasing VEGF secretion

Rho

Son

et al. 2019

Sci Rep

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Angiogenesis is involved in both normal physiological and pathological conditions. Vascular endothelial growth factor (VEGF) is a major factor for promoting angiogenesis. The current anti-VEGF therapies have limited efficacy and significant adverse effects. To find novel targets of VEGFA for angiogenesis inhibition, we performed yeast two-hybrid screening and identified calpain-6 as a novel VEGFA-interaction partner and confirmed the endogenous VEGFA–calpain-6 interaction in mammalian placenta. A domain mapping study revealed that the Gly321–Asp500 domain in calpain-6 is required for the interaction with the C-terminus of the VEGFA protein. The functional significance of the VEGFA–calpain-6 interaction was explored by assessing its effect on angiogenesis in vitro. Whereas forced overexpression of calpain-6 increased the secretion of the VEGF protein and tube formation, knockdown of calpain-6 expression abrogated the calpain-6-mediated VEGF secretion and tube formation in HUVECs. Consistent with the domain mapping result, overexpressing calpain-6 without the VEGFA-interacting domain III (Gly321–Asp500) failed to increase the secretion of VEGF protein. Our results identify calpain-6, an unconventional non-proteolytic calpain, as a novel VEGFA-interacting protein and demonstrate that their interaction is necessary to enhance VEGF secretion. Thus, calpain-6 might be a potential molecular target for angiogenesis inhibition in many diseases.

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Integrated analysis reveals candidate mRNA and their potential roles in uterine leiomyomas

Abstract: In conclusion, our study observed that a set of aberrantly expressed genes and the related biochemical pathways may lead to transformation of normal myometrium in pathological focuses.

Cited by 8 publications

References 40 publications

Bioinformatic Analysis Identifies potential key genes in the pathogenesis of uterine leiomyoma

Bioinformatic Analysis Identifies potential key genes in the pathogenesis of uterine leiomyoma

Hsa_circ_0056686, derived from cancer-associated fibroblasts, promotes cell proliferation and suppresses apoptosis in uterine leiomyoma through inhibiting endoplasmic reticulum stress

Non-proteolytic calpain-6 interacts with VEGFA and promotes angiogenesis by increasing VEGF secretion

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