Identification and Functional Validation of Differentially Expressed microRNAs in Ascites-Derived Ovarian Cancer Cells Compared with Primary Tumour Tissue

Abstract Purpose: Ovarian cancer, manifested by malignant ascites, is the most lethal gynaecological cancer. Suspended ascites-derived spheroids may contribute to ovarian cancer metastasis. MicroRNAs (miRNAs) are also associated with ovarian cancer metastasis. Here, we aimed to investigate the differentially expressed miRNAs (DE-miRNAs) in ascites-derived spheroids compared with primary tumour tissue, which may regulate ovarian cancer metastasis.Methods: The DE-miRNAs between ovarian cancer primary tumour tissues and ascites-derived spheroids were identified by GEO2R screening in dataset GSE65819. We used MiRTarBase and STRING to predict the target hub genes of DE-miRNAs and WebGestalt to perform functional analysis of hub genes. ALGGEN PROMO and TransmiR v2.0 were used to predict the common transcription factors (TFs) that potentially regulate DE-miRNAs expression. The observed differences in DE-miRNAs expression were validated with human ovarian cancer samples and ovarian cancer cell lines using PCR. The functions of DE-miRNAs on ovarian cancer progression were verified by transwell and angiogenesis assays.Results: Through bioinformatics screening and experimental validation, miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p were identified as being significantly downregulated in ascites-derived spheroids compared with primary tumour tissues. In addition, TFAP2A was identified as a potentially common upstream TF regulating the expression of the abovementioned DE-miRNAs. The overexpression of miR-199a-3p, miR-199b-3p, miR-199a-5p could inhibit ovarian cancer invasion, and the overexpression of miR-145-5p could inhibit angiogenesis.Conclusion: The downregulated expression of miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p in ascites-derived spheroids plays a key role in promoting ovarian cancer progression, which may represent novel molecules for targeted therapy for ovarian cancer.

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Identification and Functional Validation of Differentially Expressed microRNAs in Ascites-derived Ovarian Cancer Cells Compared With Primary Tumour Tissue

10.21203/rs.3.rs-51079/v2 ◽

2020 ◽

Author(s):

Yahui Jiang ◽

Tianjiao Lyu ◽

Hua Liu ◽

Lifei Shen ◽

Yiwen Shi ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Progression ◽

Cancer Metastasis ◽

Primary Tumour ◽

Malignant Ascites ◽

Differentially Expressed ◽

Tumour Tissue ◽

Ovarian Cancer Cells ◽

Hub Genes ◽

Mirnas Expression

Abstract Purpose: Ovarian cancer, manifested by malignant ascites, is the most lethal gynaecological cancer. Suspended ascites-derived spheroids may contribute to ovarian cancer metastasis. MicroRNAs (miRNAs) are also associated with ovarian cancer metastasis. Here, we aimed to investigate the differentially expressed miRNAs (DE-miRNAs) in ascites-derived spheroids compared with primary tumour tissue, which may regulate ovarian cancer metastasis. Methods: The DE-miRNAs between ovarian cancer primary tumour tissues and ascites-derived spheroids were identified by GEO2R screening in dataset GSE65819. We used MiRTarBase, TargetScanHuman7.2 and STRING to predict the target hub genes of DE-miRNAs and DAVID to perform functional analysis of hub genes. ALGGEN PROMO and TransmiR v2.0 were used to predict the common transcription factors (TFs) that potentially regulate DE-miRNAs expression. The observed differences in DE-miRNAs expression were validated with human ovarian cancer samples and ovarian cancer cell lines using PCR. The functions of DE-miRNAs on ovarian cancer progression were verified by transwell and angiogenesis assays. Results: Through bioinformatics screening and experimental validation, miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p were identified as being significantly downregulated in ascites-derived spheroids compared with primary tumour tissues. In addition, TFAP2A was identified as a potentially common upstream TF regulating the expression of the abovementioned DE-miRNAs. The overexpression of miR-199a-3p, miR-199b-3p, miR-199a-5p could inhibit ovarian cancer invasion, and the overexpression of miR-145-5p could inhibit angiogenesis. Conclusion: The downregulated expression of miR-199a-3p, miR-199b-3p, miR-199a-5p, miR-126-3p and miR-145-5p in ascites-derived spheroids plays a key role in promoting ovarian cancer progression, which may represent novel molecules for targeted therapy for ovarian cancer.

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Rhizoctonia bataticola lectin induces apoptosis and inhibits metastasis in ovarian cancer cells by interacting with CA 125 antigen differentially expressed on ovarian cells

Glycoconjugate Journal ◽

10.1007/s10719-021-10027-7 ◽

2021 ◽

Author(s):

Prajna Hegde ◽

Sindhura B.R ◽

Suhas Ballal ◽

Bale M. Swamy ◽

Shashikala R. Inamdar

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Differentially Expressed ◽

Ca 125 ◽

Ovarian Cancer Cells ◽

Rhizoctonia Bataticola ◽

Ovarian Cells ◽

Ca 125 Antigen

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Knockdown CD44 Promotes Amyloid-Beta Degradation in Ovarian Cancer Cells By Regulating CD36 Expression

10.21203/rs.3.rs-946298/v1 ◽

2021 ◽

Author(s):

Ying Xu ◽

Yunge Gao ◽

Luomeng Qian ◽

Wangyou Feng ◽

Tingting Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Amyloid Beta ◽

Functional Enrichment ◽

Differentially Expressed ◽

Receptor Interaction ◽

Ovarian Cancer Cells ◽

Cd36 Expression ◽

Skov3 Cells

Abstract Background: CD44 is highly expressed in many cancers, including ovarian cancer. Its interactions with ligands are involved in tumor progression, prognosis, and metastasis. However, the function of CD44 in the advancement of ovarian cancer remains unclear. Methods and Results: RNA sequencing was used to investigate the possible molecules and pathways regulated by CD44 in ovarian cancer to compare gene expression in CD44-knockdown SKOV3 cells and control cells. Identify the differentially expressed genes and then proceed to functional enrichment analysis. The results showed that genes differentially expressed were enriched in ECM-receptor interaction, Protein digestion and absorption, Focal adhesion, Notch signaling pathway, microRNA in cancer, and TGF-beta signaling pathway. Furthermore, the analysis of the proteins interaction network revealed the interaction between CD44 and CD36 in SKOV3 cells. Further analysis showed that CD36, a molecule that may be involved in ECM-receptor interaction, was low expressed in CD44-knockdown SKOV3 cells. And the results showed that knockdown CD44 induces amyloid-beta degradation in ovarian cancer cells by regulating CD36 expression. The analyses of the public database demonstrated that the CD36 expression was related to the clinical survival of ovarian cancer. Conclusions: Our study showed that CD44 might up-regulate the CD36 expression in ovarian cancer, thereby exerting a cancer-promoting effect.

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