The NF-κB modulated miR-194-5p/IGF1R/PPFIBP axis is crucial for the tumorigenesis of ovarian cancer

Bai, Ru; Dou, Kaikai; Wu, Yang; Ma, Yongjing; Sun, Jianmin

doi:10.7150/jca.40604

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…As shown in previous studies, miR-194-5p acted as a tumor suppressor in many cancers, such as ovarian cancer 28 , bladder cancer 29 , glioblastoma multiforme 30 . Consistent with the aforementioned literature, miR-194-5p exerts an inhibitory effect in CRC.…”

Section: Discussionsupporting

confidence: 60%

A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

et al. 2021

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Long noncoding RNAs (lncRNAs) show emerging roles in colorectal cancer (CRC) development and are considered to be involved in the potential mechanism of tumor malignancy. While Sox2 overlapping transcript (SOX2OT) has been implicated in the progression of multiple cancers, its role in CRC remains to be explored. In this study, in situ hybridization (ISH) and qRT-PCR were performed to establish the functional relationships between SOX2OT and CRC deranged in CRC tissue and cells. Subsequently, SOX2OT shRNAs vectors were transfected into CRC cells to performed loss-of-function assays to detect the potential role of SOX2OT on proliferation and metastasis in vitro and vivo. The results showed SOX2OT was an oncogene that was up-regulated in human CRC tissues and cell lines. SOX2OT silencing suppressed cell proliferation, migration, and invasion in CRC cells in vitro, and inhibited tumorigenesis in the mouse xenografts. Bioinformatic predictive analysis coupled with the dual-luciferase reporter, RNA immunoprecipitation (RIP), and functional rescue assay elucidated the mechanistic network of the SOX2OT-miR-194-5p-SOX5 axis in CRC. Mechanistically, SOX2OT acted as a competing endogenous RNA (ceRNA) to upregulate SOX5 by sponging miR-194-5p. Downregulated SOX2OT boosted miR-194-5p expression, thus decreased the protein level of SOX5, which suppresses tumorgenesis of CRC.

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Section: Discussionsupporting

confidence: 60%

A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

et al. 2021

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“…Zheng et al (46) showed that YTHDF3 as an m 1 A reader decreased invasion and migration of trophoblast by inhibiting IGF1R expression. IGF1R was also reported as an oncogene in cancers (47). So, we speculated that YTHDF3 may regulate the expression of some oncogenes in CHOL.…”

Section: Discussionmentioning

confidence: 85%

Gene Signatures and Prognostic Values of m6A Genes in Nasopharyngeal Carcinoma

Xiao

et al. 2020

Front. Oncol.

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Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high rate of local invasion and early distant metastasis. Accumulating studies suggest that N6-methyladenosine methylation (m 6 A) is closely related to tumorigenesis. However, the relationship between m 6 A-related genes and prognosis of NPC is poorly understood. Our research aims to discover the prognostic value of m 6 A RNA methylation genes in NPC. In this study, we analyzed the differentially expressed m 6 A-related genes between NPC samples and normal control samples and found that two upregulated genes (YTHDF3 and IGF2BP2) and one downregulated gene (METTL3) were overlapped in GSE68799 and GSE53819. Next, we found that high expression of IGF2BP1 and low expression of METTL3 and YTHDF3 in NPC patients showed poor progression-free survival (PFS). Subsequently, the four m 6 A genes were selected for consensus cluster analysis, and risk models were established. The risk signature, using three genes (GF2BP1 + IGF2BP2 + METTL3), was an independent prognostic factor and predicts the clinicopathological features of NPC. Additionally, the GO, KEGG analysis, and CIBERSORT algorithm revealed that the risk signature was closely associated to immune infiltration in NPC. Finally, the expression and clinical significance of METTL3 were successfully validated in NPC tissues using immunohistochemical techniques. In conclusion, our finding revealed the potential role of m 6 A modification in NPC, providing novel insight into NPC prognosis and therapeutic strategies.

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“…The reduced expression of miR-194-5p promotes IGF1R and PPFIBP expression, promoting OC progression. NF-κB binds to the miR-194-5p promoter and negatively regulates miR-194-5p expression [ 53 ]. TPM1 overexpression has been demonstrated to promote cell apoptosis, inhibit migration, and its expression is correlated to OSCC prognosis [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of MMP-1 in osteosarcoma cells contribute to cancer progression, metastasis, and stem-like properties [ 35 ]. In addition, a recent study has demonstrated that PPFIBP1 contributes to the tumorigenesis of OC [ 53 ]. MMP1 and PPIFIB1 expression have decreased with increasing drug time exposure that indicates MMP1 and PPIFIB1 expression might be associated with carboplatin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and verification of molecular targets in ovarian cancer stem-like cells

Behera

Ashraf

Srivastava

et al. 2020

Heliyon

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Background Epithelial ovarian cancer (EOC) is a lethal and aggressive gynecological malignancy. Despite recent advances, existing therapies are challenged by a high relapse rate, eventually resulting in disease recurrence and chemoresistance. Emerging evidence indicates that a subpopulation of cells known as cancer stem-like cells (CSLCs) exists with non-tumorigenic cancer cells (non-CSCs) within a bulk tumor and is thought to be responsible for tumor recurrence and drug-resistance. Therefore, identifying the molecular drivers for cancer stem cells (CSCs) is critical for the development of novel therapeutic strategies for the treatment of EOC. Methods Two gene datasets were downloaded from the Gene Expression Omnibus (GEO) database based on our search criteria. Differentially expressed genes (DEGs) in both datasets were obtained by the GEO2R web tool. Based on log 2 (fold change) >2, the top thirteen up-regulated genes and log 2 (fold change) < -1.5 top thirteen down-regulated genes were selected, and the association between their expressions and overall survival was analyzed by OncoLnc web tool. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways analysis, and protein-protein interaction (PPI) networks were performed for all the common DEGs found in both datasets. SK-OV-3 cells were cultured in an adherent culture medium and spheroids were generated in suspension culture with CSCs specific medium. RNA from both cell population was extracted to validate the selected DEGs expression by q-PCR. Growth inhibition assay was performed in SK-OV-3 cells after carboplatin treatment. Results A total of 200 DEGs, 117 up-regulated and 83 down-regulated genes were commonly identified in both datasets. Analysis of pathways and enrichment tests indicated that the extracellular matrix part, cell proliferation, tissue development, and molecular function regulation were enriched in CSCs. Biological pathways such as interferon-alpha/beta signaling, molecules associated with elastic fibers, and synthesis of bile acids and bile salts were significantly enriched in CSCs. Among the top 13 up-regulated and down-regulated genes, MMP1 and PPFIBP1 expression were associated with overall survival. Higher expression of ADM, CXCR4, LGR5, and PTGS2 in carboplatin treated SK-OV-3 cells indicate a potential role in drug resistance. Conclusions The molecular signature and signaling pathways enriched in ovarian CSCs were identified by bioinformatics analysis. This analysis could provide further research ideas to find the new mechanism and novel potential therapeutic targets for ovarian CSCs.

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The NF-κB modulated miR-194-5p/IGF1R/PPFIBP axis is crucial for the tumorigenesis of ovarian cancer

Cited by 14 publications

References 28 publications

A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

A novel lncRNA SOX2OT promotes the malignancy of human colorectal cancer by interacting with miR-194-5p/SOX5 axis

Gene Signatures and Prognostic Values of m6A Genes in Nasopharyngeal Carcinoma

Bioinformatics analysis and verification of molecular targets in ovarian cancer stem-like cells

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