Cellular Mechanism of Gene Mutations and Potential Therapeutic Targets in Ovarian Cancer

Guo, Tao; Xue, Dong; Xie, Shanli; Zhang, Ling; Zeng, Peibin; Zhang, Lin

doi:10.2147/cmar.s292992

Cited by 35 publications

(41 citation statements)

References 163 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These include the promotion of a cancer stem cell phenotype, improved DNA repair mechanisms linked to therapeutic resistance, and regulation of multiple signaling processes that drive prometastatic EMT [ 78 , 79 , 80 ]. KRAS also has an ongogenic function in ovarian cancer, as constitutive activation of this small GTPase by gene mutations activates uncontrolled ovarian cancer cell proliferation via activation of the mitogen axctivated protein kinase (MAPK)/ extracellular signal regulated kinase (ERK) pathway, a signaling pathway that is also regulated by HMGA2 [ 78 , 81 ]. Therefore, downregulation of HMGA2 and KRAS by let-7d could exert an anti-oncogenic effect in ovarian cancer.…”

Section: Let-7d and Ovarian Cancermentioning

confidence: 99%

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

Santis¹,

Götte²

2021

IJMS

View full text Add to dashboard Cite

microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

show abstract

Section: Let-7d and Ovarian Cancermentioning

confidence: 99%

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

Santis¹,

Götte²

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In recurrent low-grade serous ovarian cancer, the frequency of KRAS mutations is as high as 70%. 47 Moreover, Martinez-Outschoorn et al observed that RAS mutations can reprogram the metabolism of cancer cells, 48 which explains the potential role of KRAS signaling in ovarian cancer drug resistance. Our data indicate that the upregulation of the KRAS pathway may affect oxidative phosphorylation and fatty acid metabolism in platinum-resistant cells, leading to metabolic reprogramming of tumor cells.…”

mentioning

confidence: 99%

Identification of Three Potential Prognostic Genes in Platinum-Resistant Ovarian Cancer via Integrated Bioinformatics Analysis

Zhang¹,

Xuan²,

Bai³

et al. 2021

CMAR

View full text Add to dashboard Cite

“…Specific gene mutations contribute to the development and pathogenesis of ovarian cancer; gene mutations are related to the clinical phenotype of cancers, suggesting the critical role of the loci of gene mutations as prognostic and therapeutic targets [ 37 – 39 ]. PIK3CA, TP53, BRCA1/2 , and KRAS are highly associated with epithelial ovarian cancer [ 39 ]. PIK3CA mutations are prevalent in ovarian clear cell carcinoma and endometrioid ovarian carcinoma [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis

Sohn

2022

BMC Cancer

View full text Add to dashboard Cite

Background Ovarian cancer is the most lethal gynecologic disease and is one of the most commonly diagnosed cancers among women worldwide. The phosphatidylinositol 3-kinase (PI3K) family plays an important regulatory role in various cancer signaling pathways, including those involved in ovarian cancer development; however, its exact function remains to be fully understood. We conducted this study to understand the role of P13K in the molecular mechanisms underlying ovarian cancer development. Methods To determine the differential gene expression of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, in normal, tumor, and metastatic ovary tissues, TNM plotter analysis was performed. The microarray dataset GSE53759 was downloaded from Gene Expression Omnibus. ROC plotter analysis was conducted to understand the potential of PIK3R3 as a predictive marker for effectiveness of therapy in ovarian cancer. muTarget was used to identify mutations that alter PIK3R3 expression in ovarian cancer. To determine the interacting partners for PIK3R3 in ovarian tissues, the interactome-atlas tool was used. The Kyoto encyclopedia of genes and genomes (KEGG) analysis was conducted to identify the pathways in which these interacting partners were primarily enriched. Results PIK3R3 was overexpressed in ovarian and metastatic tumors. Elevated PIK3R3 levels were observed in ovarian cancer stem cells, wherein inhibiting PIK3R3 expression significantly reduced the size of ovarian cancer spheroids. Treatment of ovarian cancer stem cells with PF-04691502 (10 μM), an inhibitor of both PI3K and mTOR kinases, also reduced the size of spheroids and the level of OCT4. PIK3R3 was highly expressed in ovarian cancer with several somatic mutations and was predicted better outcomes in patients undergoing Avastin® chemotherapy using bioinformatic tool. Protein interaction analysis showed that PIK3R3 interacts with 157 genes, including GRB2, EGFR, ERBB3, PTK2, HCK, IGF1R, YES1, and PIK3CA, in the ovary. KEGG enrichment analysis revealed that the interacting partners of PIK3R3 are involved in the ErbB signaling pathway, proteoglycans in cancer, FoxO, prolactin, chemokine, and insulin signaling pathways. Conclusions PIK3R3 plays a pivotal role in ovarian cancer development and is therefore a potential candidate for developing novel therapeutic approaches.

show abstract

Cellular Mechanism of Gene Mutations and Potential Therapeutic Targets in Ovarian Cancer

Cited by 35 publications

References 163 publications

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract

Identification of Three Potential Prognostic Genes in Platinum-Resistant Ovarian Cancer via Integrated Bioinformatics Analysis

PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis

Contact Info

Product

Resources

About