• diagnostic biomarkers
• endometrial cancer
• metastatic biomarkers
• miRNAs
• ovarian cancer
• vaginal cancer
• vulvar cancer

• Humans
• Female
• Biomarkers, Tumor/genetics
• Genital Neoplasms, Female/genetics
• Genital Neoplasms, Female/diagnosis
• Genital Neoplasms, Female/pathology
• Genital Neoplasms, Female/metabolism
• MicroRNAs/genetics
• MicroRNAs/blood
• Prognosis
• Neoplasm Metastasis
• Gene Expression Regulation, Neoplastic

• 9595/19.06.2024 Hellenic Society of Medical Oncology (HeSMO)

• aberrant expression
• biomarker
• diagnosis
• gynaecologic malignancy
• microRNA
• ovarian cancer

• Biomarker
• Diagnostic biomarker
• Ovarian cancer
• Prognostics
• Therapeutic strategy
• microRNA

• AKT
• bioactive substance
• cell function
• miRNA
• natural products

• Humans
• Biological Products/pharmacology
• MicroRNAs/genetics
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/metabolism
• Proto-Oncogene Proteins c-akt/drug effects
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction/genetics

• MOST 111-2320-B-037-015-MY3; MOST 110-2314-B-037-074-MY3 Ministry of Science and Technology
• KMU-DK(A)111008 Kaohsiung Medical University
• KMU-TC108A04 Kaohsiung Medical University Research Center

Patients with ovarian cancer have a very poor chance of long-term survival, usually due to advanced disease at the time of diagnosis. Emerging evidence suggests that extracellular vesicles contain noncoding RNAs such as microRNAs, piwiRNAs, circular RNAs, and long noncoding RNAs, with regulatory effects on ovarian cancer. In this review, we focus on ovarian cancer-associated circular RNA shuttled by extracellular vesicles as mediators of cancer progression and novel biomarkers in liquid biopsy. We propose a circular-RNA–microRNA-mRNA code that can reveal the regulatory network created by extracellular vesicles, noncoding RNAs, and mRNAs in ovarian cancer. Future research in this field will help to identify novel diagnostic biomarkers and druggable therapeutic targets, which will ultimately benefit patients.

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies in females worldwide. OC is frequently diagnosed at an advanced stage due to a lack of specific symptoms and effective screening tests, resulting in a poor prognosis for patients. Age, genetic alterations, and family history are the major risk factors for OC pathogenesis. Understanding the molecular mechanisms underlying OC progression, identifying new biomarkers for early detection, and discovering potential targets for new drugs are urgent needs. Liquid biopsy (LB), used for cancer detection and management, consists of a minimally invasive approach and practical alternative source to investigate tumor alterations by testing extracellular vesicles (EVs), circulating tumor cells, tumor-educated platelets, and cell-free nucleic acids. EVs are nanosize vesicles shuttling proteins, lipids, and nucleic acids, such as DNA, RNA, and non-coding RNAs (ncRNAs), that can induce phenotypic reprogramming of target cells. EVs are natural intercellular shuttles for ncRNAs, such as microRNAs (miRNAs) and circular-RNAs (circRNAs), known to have regulatory effects in OC. Here we focus on the involvement of circRNAs and miRNAs in OC cancer progression. The circRNA-microRNA-mRNA axis has been investigated with Circbank and miRwalk analysis, unraveling the intricate and detailed regulatory network created by EVs, ncRNAs, and mRNAs in OC.

Among many gynecological malignancies ovarian cancer is the most prominent and leading cause of female mortality worldwide. Despite extensive research, the underlying cause of disease progression and pathology is still unknown. In the progression of ovarian cancer different non-coding RNAs have been recognized as important regulators. The biology of ovarian cancer which includes cancer initiation, progression, and dissemination is found to be regulated by different ncRNA. Clinically ncRNA shows high prognostic and diagnostic importance.

In this review, we prioritize the role of different non-coding RNA and their perspective in diagnosis as potential biomarkers in the case of ovarian cancer. Summary of some of the few miRNAs involved in epithelial ovarian cancer their expression and clinical features are being provided in the table. Also, in cancer cell proliferation, apoptosis, invasion, and migration abnormal expression of piRNAs are emerging as a crucial regulator hence the role of few piRNAs is being given. Both tRFs and tiRNAs play important roles in tumorigenesis and are promising diagnostic biomarkers and therapeutic targets for cancer. lncRNA has shown a leading role in malignant transformation and potential therapeutic value in ovarian cancer therapy.

Hence in this review we demonstrated the role of different ncRNA that play an important role in serving strong potential as a therapeutic approach for the treatment of ovarian cancer.

• Gynecological malignancies
• Long coding RNA
• Ovarian cancer
• Small non-coding-RNA
• microRNAs (miRNAs)
• tRNA-derived small RNAs

Chemotherapy resistance, especially platinum resistance, is the main cause of poor prognosis of ovarian cancer. It is of great urgency to find molecular markers and mechanism related to platinum resistance in ovarian cancer.

One mRNA dataset (GSE28739) and one miRNA dataset (GSE25202) were acquired from Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) between platinum-resistant and platinum-sensitive ovarian cancer patients. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed using the DAVID to present the most visibly enriched pathways. Protein–protein interaction (PPI) of these DEGs was constructed based on the information of the STRING database. Hub genes related to platinum resistance were visualized by Cytoscape software. Then, we chose seven interested hub genes to further validate using qRT-PCR in A2780 ovarian cancer cell lines. And, at last, the TF-miRNA-target genes regulatory network was predicted and constructed using miRNet software.

A total of 63 upregulated DEGs, 124 downregulated DEGs, four upregulated miRNAs and six downregulated miRNAs were identified. From the PPI network, the top 10 hub genes were identified, which were associated with platinum resistance. Our further qRT-PCR showed that seven hub genes (BUB1, KIF2C, NUP43, NDC80, NUF2, CCNB2 and CENPN) were differentially expressed in platinum-resistant ovarian cancer cells. Furthermore, the upstream transcription factors (TF) for upregulated DE-miRNAs were SMAD4, NFKB1, SMAD3, TP53 and HNF4A. Three overlapping downstream target genes (KIF2C, STAT3 and BUB1) were identified by miRNet, which was regulated by hsa-miR-494.

The TF-miRNA–mRNA regulatory pairs, that is TF (SMAD4, NFKB1 and SMAD3)-miR-494-target genes (KIF2C, STAT3 and BUB1), were established. In conclusion, the present study is of great significance to find the key genes of platinum resistance in ovarian cancer. Further study is needed to identify the mechanism of these genes in ovarian cancer.

• Expression profiling data
• Hub genes
• Ovarian cancer
• Platinum resistance

• Apoptosis
• T cell
• Trichostatin A.
• epigenetics
• histone deacetylases
• leukemia
• microRNA-494

Sirtuin 1 (SIRT1), a member of the sirtuin protein family, is a nicotinamide adenine dinucleotide (NAD⁺)-dependent type III histone deacetylase and mono-ADP-ribosyltransferase. SIRT1 can deacetylate histones (H1, H3, and H4) and non-histone proteins, and it is widely involved in various physiological and pathological processes in the body, including metabolism, aging, transcription, DNA damage and repair, apoptosis, cell cycle regulation, inflammation and cancer. Research has shown that SIRT1 is involved in tumorigenesis, tumor metastasis and chemotherapy resistance, but it exerts opposing effects and plays different roles in different pathogenic processes. Recent studies have demonstrated that SIRT1 may be implicated in the pathogenesis, development, treatment and prognosis of tumors; however, its role in gynecological tumors remains elusive. The aim of the present review was to summarize the pathogenic roles of SIRT1 in cancer, and to provide what is, to the best of our knowledge, the first review of recent advances involving SIRT1 in cervical cancer, endometrial cancer (EC) and ovarian cancer (OC). In addition, the critical research gaps regarding SIRT1, particularly its potential involvement in the concurrence of EC and cervical cancer and its antagonistic effect against poly(ADP-ribose) polymerase inhibitors in OC, were highlighted.

• sirtuin 1
• cervical cancer
• endometrial cancer
• ovarian cancer
• poly(ADP‑ribose) polymerase inhibitors

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and the major cause of death is mainly attributed to metastasis. MicroRNAs (miRNAs) are a group of small non-coding RNAs that exert important regulatory functions in many biological processes through their effects on regulating gene expression. In most cases, miRNAs interact with the 3′ UTRs of target mRNAs to induce their degradation and suppress their translation. Aberrant expression of miRNAs has been detected in EOC tumors and/or the biological fluids of EOC patients. Such dysregulation occurs as the result of alterations in DNA copy numbers, epigenetic regulation, and miRNA biogenesis. Many studies have demonstrated that miRNAs can promote or suppress events related to EOC metastasis, such as cell migration, invasion, epithelial-to-mesenchymal transition, and interaction with the tumor microenvironment. In this review, we provide a brief overview of miRNA biogenesis and highlight some key events and regulations related to EOC metastasis. We summarize current knowledge on how miRNAs are dysregulated, focusing on those that have been reported to regulate metastasis. Furthermore, we discuss the role of miRNAs in promoting and inhibiting EOC metastasis. Finally, we point out some limitations of current findings and suggest future research directions in the field.

• epithelial ovarian cancer
• metastasis
• microRNAs (miRNAs)

• Carcinoma, Ovarian Epithelial/metabolism
• Carcinoma, Ovarian Epithelial/pathology
• Cell Line, Tumor
• Cell Movement
• Epigenesis, Genetic
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• MicroRNAs/physiology
• Neoplasm Metastasis
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/pathology
• Tumor Microenvironment

• biomarker
• circulating
• microRNA
• ovarian cancer
• prognosis
• ribonucleic
• tissue.

• Diagnosis
• Ovarian cancer
• Prognosis
• miRNA

• AKT
• AMPK/TSC/mTOR pathway
• GC-2spd cells
• Silica nanoparticles
• miRNA-494

• Animals
• Autophagy/drug effects
• Cell Line
• Down-Regulation
• Male
• Mice
• MicroRNAs/genetics
• Nanoparticles/toxicity
• Proto-Oncogene Proteins c-akt/metabolism
• Semen Analysis
• Silicon Dioxide/toxicity
• Spermatocytes
• Spermatozoa/drug effects
• Spermatozoa/pathology
• Up-Regulation

Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays critical roles in the genesis and development of human cancers.

To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.

Expression levels of IGF2BP1 and microRNA-494 (miR-494) were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot. The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed. The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo. Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the post-transcriptional regulation of IGF2BP1 by miR-494.

We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients. We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway. Mechanistically, we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer. Furthermore, we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.

Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.

• Pancreatic cancer
• Insulin-like growth factor 2 mRNA-binding protein 1
• Proliferation
• MicroRNA-494

• Animals
• Carcinogenesis/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Datasets as Topic
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Male
• Mice
• MicroRNAs/metabolism
• Middle Aged
• Pancreas/pathology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Prognosis
• Proto-Oncogene Proteins c-akt/metabolism
• RNA-Binding Proteins/genetics
• Signal Transduction/genetics
• Up-Regulation
• Xenograft Model Antitumor Assays

• Cholangiocarcinoma
• Epithelial-mesenchymal transition
• Lymph node metastasis
• MicroRNA-494
• WDHD1

• Aged
• Animals
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/metabolism
• Bile Duct Neoplasms/pathology
• Cell Line, Tumor
• Cell Proliferation
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/metabolism
• Cholangiocarcinoma/pathology
• DNA-Binding Proteins/genetics
• DNA-Binding Proteins/metabolism
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis/pathology
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Middle Aged
• Signal Transduction
• Time Factors
• Transfection
• Tumor Burden
• Up-Regulation
• Xenograft Model Antitumor Assays

MiR-494 plays an important role in several types of human cancers, including non-small cell lung cancer (NSCLC). Although the role of miR-494 has been investigated in several studies, the expression profile and underlying mechanism are still poorly understood. In this study, we found that overexpression of miR-494 promoted the proliferation and colony formation of NSCLC cells and reduced their sensitivity to cisplatin-induced apoptosis. By using microarray and Dual luciferase reporter assays, we further showed that caspase-2 (CASP2) is a functional target of miR-494, and the expression of CASP2 is inversely associated with miR-494 in vitro. In addition, miR-494 promoted the proliferation and colony formation of NSCLC cells and reduced their sensitivity to cisplatin-induced apoptosis by targeting CASP2. Therefore, our results suggest that miR-494 plays an oncomiR role in NSCLC cells and may be a candidate biomarker for malignant transformation and a therapeutic target of NSCLC.

It may be possible to discover new diagnostic or therapeutic peptides or proteins from blood plasma by using liquid chromatography and tandem mass spectrometry to identify, quantify and compare the peptides cleaved ex vivo from different clinical populations. The endogenous tryptic peptides of ovarian cancer plasma were compared to breast cancer and female cancer normal controls, other diseases with their matched or normal controls, plus ice cold plasma to control for pre-analytical variation.

The endogenous tryptic peptides or tryptic phospho peptides (i.e. without exogenous digestion) were analyzed from 200 μl of EDTA plasma. The plasma peptides were extracted by a step gradient of organic/water with differential centrifugation, dried, and collected over C18 for analytical HPLC nano electrospray ionization and tandem mass spectrometry (LC–ESI–MS/MS) with a linear quadrupole ion trap. The endogenous peptides of ovarian cancer were compared to multiple disease and normal samples from different institutions alongside ice cold controls. Peptides were randomly and independently sampled by LC–ESI–MS/MS. Precursor ions from peptides > E4 counts were identified by the SEQUEST and X!TANDEM algorithms, filtered in SQL Server, before testing of frequency counts by Chi Square (χ²), for analysis with the STRING algorithm, and comparison of precursor intensity by ANOVA in the R statistical system with the Tukey-Kramer Honestly Significant Difference (HSD) test.

Peptides and/or phosphopeptides of common plasma proteins such as HPR, HP, HPX, and SERPINA1 showed increased observation frequency and/or precursor intensity in ovarian cancer. Many cellular proteins showed large changes in frequency by Chi Square (χ² > 60, p < 0.0001) in the ovarian cancer samples such as ZNF91, ZNF254, F13A1, LOC102723511, ZNF253, QSER1, P4HA1, GPC6, LMNB2, PYGB, NBR1, CCNI2, LOC101930455, TRPM5, IGSF1, ITGB1, CHD6, SIRT1, NEFM, SKOR2, SUPT20HL1, PLCE1, CCDC148, CPSF3, MORN3, NMI, XTP11, LOC101927572, SMC5, SEMA6B, LOXL3, SEZ6L2, and DHCR24. The protein gene symbols with large Chi Square values were significantly enriched in proteins that showed a complex set of previously established functional and structural relationships by STRING analysis. Analysis of the frequently observed proteins by ANOVA confirmed increases in mean precursor intensity in ZFN91, TRPM5, SIRT1, CHD6, RIMS1, LOC101930455 (XP_005275896), CCDC37 and GIMAP4 between ovarian cancer versus normal female and other diseases or controls by the Tukey–Kramer HSD test.

Here we show that separation of endogenous peptides with a step gradient of organic/water and differential centrifugation followed by random and independent sampling by LC–ESI–MS/MS with analysis of peptide frequency and intensity by SQL Server and R revealed significant difference in the ex vivo cleavage of peptides between ovarian cancer and other clinical treatments. There was striking agreement between the proteins discovered from cancer plasma versus previous biomarkers discovered in tumors by genetic or biochemical methods. The results indicate that variation in plasma proteins from ovarian cancer may be directly discovered by LC–ESI–MS/MS that will be a powerful tool for clinical research.

The online version of this article (10.1186/s12014-018-9215-z) contains supplementary material, which is available to authorized users.

• Chi Square test and ANOVA
• Discovery of variation
• Electrospray ionization tandem mass spectrometry
• Human EDTA plasma
• LC–ESI–MS/MS
• Linear quadrupole ion trap
• Nano chromatography
• Organic extraction
• Ovarian cancer
• Random and independent sampling
• SQL SERVER & R

• Breast cancer
• Cell cycle
• Node-negative
• Prognosis
• Proliferation
• miRNA

The class III histone deacetylase silent information regulator 1 (SIRT1) is frequently overexpressed in a variety of tumors, including lung cancer; however, its regulatory mechanisms are largely unknown. In this study, we found that an inconsistent trend between SIRT1 protein and mRNA levels in human lung cancer tissues, suggesting that a post-transcriptional mechanism may involved in SIRT1 regulation. Because microRNAs are important post-transcriptional regulators of gene expression, candidate miRNAs that could potentially bind SIRT1 were gained through bioinformatics analyses. We further experimentally validated SIRT1 as the direct target of miR-30a by evaluating SIRT1 expression in lung cancer cells after the overexpression or knockdown of miR-30a and by luciferase assay. Moreover, we showed that miR-30a inhibited proliferation, invasion and promoted apoptosis of lung cancer cells by inhibiting SIRT1 in vitro and in vivo. Taken together, this study identified a new regulatory axis in which miR-30a and SIRT1 regulate the proliferation, invasion and apoptosis of lung cancer cells and lung tumorigenesis.

• SIRT1
• apoptosis
• invasion
• miR-30a
• proliferation