Roles of microRNAs in Ovarian Cancer Tumorigenesis: Two Decades Later, What Have We Learned?

Alshamrani, Ali A.

doi:10.3389/fonc.2020.01084

Cited by 59 publications

(43 citation statements)

References 228 publications

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“…However, it was still lack of an efficient and sensitive method to detect OvCa at early stages. 19 The expression profile of circRNAs had been identified in five paired DDP-sensitive and DDP-resistant tissues of OvCa patients using microarray analysis. 20 Here, we further investigated the expression and contribution of circHIPK2 in DDP-resistant OvCa cells both in vitro and in vivo, as well as the ceRNA pathway.…”

Section: Discussionmentioning

confidence: 99%

CircHIPK2 Contributes to DDP Resistance and Malignant Behaviors of DDP-Resistant Ovarian Cancer Cells Both in vitro and in vivo Through circHIPK2/miR-338-3p/CHTOP ceRNA Pathway

Cao¹,

Xie²,

Li³

et al. 2021

OTT

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Background: Cisplatin (DDP) is standard-of-care and first-line management for ovarian cancer (OvCa). Circular RNA HIPK2 (circHIPK2) is abnormally upregulated in serum of OvCa patients. However, its role in DDP resistance remains unclear. Methods: Expression of cirHIPK2, microRNA (miR)-338-3p and chromatin target of protein arginine methyltransferase (CHTOP) was detected by quantitative reverse transcription PCR and Western blotting. Functional experiments were performed using cell counting kit-8 assay, flow cytometry, transwell assays, Western blotting, and xenograft experiment. The interaction among cirHIPK2, miR-338-3p and CHTOP was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results: Expression of circHIPK2 and CHTOP was upregulated, and miR-338-3p was downregulated in human DDP-resistant OvCa tumors and cells. Blocking circHIPK2 could promote apoptosis and suppress the 50% inhibitory concentration (IC50) of DDP, cell proliferation, cell cycle entrance, migration and invasion in SKOV3/DDP and A2780/DDP cells. Allied with that was decreased B cell lymphoma (Bcl)-2, matrix metalloproteinase 2 (MMP2) and MMP9 levels, and increased Bcl-2-associated X protein (Bax) level. Similarly, overexpression of miR-338-3p functioned suppressive role in SKOV3/DDP and A2780/DDP cells. MiR-338-3p was a target for circHIPK2, and CHTOP was targeted by miR-338-3p, whereas silencing miR-338-3p counteracted the role of circHIPK2 knockdown, and restoring CHTOP either cancelled miR-338-3p role. The growth of A2780/DDP cells in nude mice was restrained by silencing circHIPK2 under DDP treatment or not. Conclusion: CircHIPK2 might be a tumor promoter in OvCa and was associated with DDP resistance. Silencing circHIPK2 might suppress DDP-resistant OvCa through regulating miR-338-3p/CHTOP axis.

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Section: Discussionmentioning

confidence: 99%

CircHIPK2 Contributes to DDP Resistance and Malignant Behaviors of DDP-Resistant Ovarian Cancer Cells Both in vitro and in vivo Through circHIPK2/miR-338-3p/CHTOP ceRNA Pathway

Cao¹,

Xie²,

Li³

et al. 2021

OTT

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“…The IPA analysis identified several members of the micro-RNAs as potential upstream regulators of the cathine and cathinone. These micro-RNAs have previously been reported to have different important roles in ovarian cancer regulation, prognosis, and/or diagnosis ( Alshamrani, 2020 ; Aziz et al, 2020 ; Ferreira et al, 2020 ). Hence, our present analysis could provide potential directions for future studies on the further elucidation of these micro-RNAs’ regulations of the cellular and molecular events induced by khat.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells

et al. 2021

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Khat (Catha edulis (Vahl) Endl.) is an evergreen flowering shrub used as a stimulant in many regions worldwide including East Africa, the Arabian Peninsula, Europe, and the United States. Chewing leaves of khat induces excitement and euphoria, which are primarily attributed to two major constituents, cathinone and cathine. Khat also contains other important constituents such as cathedulins. A considerable number of studies reported side effects induced by the khat extracts to both embryos and adults. These include teratogenicity and developmental retardation, oral cancer and ulcers, high blood pressure, and myocardial infarction. So far, little attention has been paid to the effects of khat extracts on the molecular signaling interactions. We aimed in this study to investigate this through evaluating the effects of khat extracts on SKOV3, a human ovarian adenocarcinoma cell line. We show, by in vitro assays, that khat induces several cellular defects including reduced cell size, cell membrane damage, and apoptosis. At high khat extract concentrations, the cell metabolic activity, cell cycle, and cellular proliferation were affected. RT-qPCR analysis showed an increase in the gene expression of the apoptotic marker BAX, the tumor suppressor p53, and the inflammatory cytokine IL-6. Protein expression analysis by immunostaining showed downregulation of β-catenin, E-cadherin, and Ki-67 and upregulation of FZD8 and SPRY2, suggesting that Wnt and FGF signaling were implicated. SwissTargetPrediction in silico analysis showed that khat constituents cathine, cathinone, catheduline K2, and catheduline E5 bind to family A G-protein-coupled receptor, cause many neurological diseases and disorders such as Alzheimer's, schizophrenia, depression, and anxiety, and induce many ovarian cancer-related diseases. The analysis also showed that important signaling pathways such as CREB, Wnt, FGF, IL-6, and ERK/MAPK, and that of the endometrial cancer, and cell cycle were implicated. Upstream regulators of cathine and cathinone were found to potentially target several molecules including interleukin-8, MMP2, PLAU, and micro-RNAs. In conclusion, khat induces significant cellular and molecular changes that could potentially cause a wide range of serious diseases and syndromes. Such an impact could have a heavy burden on the health care system in the countries where khat is consumed.

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“…They can function either as an oncogene or a tumor suppressor and their expressions in cancer cells are deregulated [136]. The miRNA expression profile for each OC subtype is reported to be distinct, with a subset of miRNAs downregulated or upregulated [137]. The miRNA signatures identified in various cancer types are being investigated for their utility as cancer biomarkers in tumor diagnosis, prognosis and therapeutic outcome.…”

Section: Role Of Mirnas In Ovarian Cancermentioning

confidence: 99%

Ovarian Cancer: Molecular Classification and Targeted Therapy

Ravindran¹,

Choudhary²

2021

Ovarian Cancer - Updates in Tumour Biology and Therapeutics [Working Title]

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Ovarian cancer is the deadliest gynecological cancer among women with an overall 5-year survival rate below 50% due to its asymptomatic nature, diagnosis at advanced stages, and a high recurrence rate after standard therapy in 70% of cases. Ovarian cancers are heterogenous cancers where each subtype possesses a varied morphology and biologic behavior. Accumulating evidence has identified each of these subtypes characterized with specific pathways activated in each along with specific gene alterations. For example, high-grade serous ovarian cancer is characterized by universal TP53 mutation, mucinous ovarian cancer with KRAS mutation and clear cell or endometrioid ovarian cancers with ARID1A mutations. With the current focus of molecular-targeted therapies for cancer, such druggable markers serve as excellent targets for precision therapy and combination therapy. This chapter, provides an overview of the critical molecular pathways activated in the ovarian cancer subtypes with its druggable targets studied in ovarian cancer. We also highlight the implications of miRNAs in chemoresistance and sensitivity in the regulation of ovarian cancer.

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Roles of microRNAs in Ovarian Cancer Tumorigenesis: Two Decades Later, What Have We Learned?

Cited by 59 publications

References 228 publications

CircHIPK2 Contributes to DDP Resistance and Malignant Behaviors of DDP-Resistant Ovarian Cancer Cells Both in vitro and in vivo Through circHIPK2/miR-338-3p/CHTOP ceRNA Pathway

CircHIPK2 Contributes to DDP Resistance and Malignant Behaviors of DDP-Resistant Ovarian Cancer Cells Both in vitro and in vivo Through circHIPK2/miR-338-3p/CHTOP ceRNA Pathway

Unraveling the Catha edulis Extract Effects on the Cellular and Molecular Signaling in SKOV3 Cells

Ovarian Cancer: Molecular Classification and Targeted Therapy

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