MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

Chen, San-Nung; Chang, Renin; Lin, Lie Chwen; Chern, Chyi-Uei; Tsai, Hsiao Wen; Wen, Zhi‐Hong; Li, Yi-Han; Li, Chia-Jung; Tsui, Kuan‐Hao

doi:10.3390/ijerph16091510

Cited by 105 publications

(91 citation statements)

References 85 publications

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“…miR-200 expression levels corroborated with disease recurrence and survival rates, predicting poor outcomes when low levels were detected [135]. Moreover, the miR-200 cluster was also found to be involved in the inhibition of angiogenesis by targeting IL-8 and CXCL-1 produced by the tumor cells [134]. Providing proof of this, researchers transferred miR-200 in tumor epithelium, resulting in a critical decrease in angiogenesis and tumor metastasis [155].…”

Section: Mirnas In Ovarian Cancermentioning

confidence: 90%

“…Studies on the presence of miRNAs in various malignancies have shown that by inhibiting the expression of proteins like HMGA2, RAS, c-Myc, and cdk6, the let-7 family had a suppressing effect on tumor growth and cell invasion [137,138]. One of its constituents, let-7b, was proved to inhibit tumor growth, both in vitro and in vivo, while low levels of let-7f were detected in those ovarian cancer cells that had metastatic abilities and high invasion capabilities, further endorsing the supposition that it might play a suppressing role in tumor invasion and metastasis [134,138]. Also inhibiting metastasis, miR-183 and miR-22 were highly expressed in low metastatic ovarian cancer [139].…”

Section: Mirnas In Ovarian Cancermentioning

confidence: 95%

“…Other upregulated miRNAs in ovarian cancer tissues are miR-199a, miR-200a, miR-200b, miR-200 [132] and miR-200c, the latter being highly expressed only in the serous epithelial type [133]. miR-200 family was found to inhibit the transcriptional inhibitors of E-cadherin, ZEB1, and ZEB2, thus promoting E-cadherin expression and the transformation into epithelial cells of mesenchymal cells [134]. In addition, by decreasing the expression of miR-200a, ovarian cancer cells underwent epithelial-mesenchymal transition (EMT), leading to cell invasion and metastasis [134,135].…”

Section: Mirnas In Ovarian Cancermentioning

confidence: 99%

“…miR-200 family was found to inhibit the transcriptional inhibitors of E-cadherin, ZEB1, and ZEB2, thus promoting E-cadherin expression and the transformation into epithelial cells of mesenchymal cells [134]. In addition, by decreasing the expression of miR-200a, ovarian cancer cells underwent epithelial-mesenchymal transition (EMT), leading to cell invasion and metastasis [134,135]. miR-200 expression levels corroborated with disease recurrence and survival rates, predicting poor outcomes when low levels were detected [135].…”

Section: Mirnas In Ovarian Cancermentioning

confidence: 99%

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miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

848

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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Section: Mirnas In Ovarian Cancermentioning

confidence: 90%

Section: Mirnas In Ovarian Cancermentioning

confidence: 95%

Section: Mirnas In Ovarian Cancermentioning

confidence: 99%

Section: Mirnas In Ovarian Cancermentioning

confidence: 99%

See 2 more Smart Citations

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

848

583

View full text Add to dashboard Cite

show abstract

“…MicroRNAs (miRNAs) are short non-coding, single-strand RNAs that suppress gene expression by binding to the 3'-untranslated region of their target mRNAs (7). Recently, several studies reported different miRNAs that play important roles in the pathogenesis of various human cancers as onco-miRNAs or tumor suppressor miRNAs (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR‑18a‑3p reduces proliferation of mesothelioma cells and sensitizes them to cisplatin

et al. 2020

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Malignant pleural mesothelioma is a notorious human malignancy. Despite combination chemotherapy with cisplatin and pemetrexed, the majority of patients with advanced malignant pleural mesothelioma have a poor prognosis. MicroRNAs (miRNAs/miRs) are short non-coding RNAs that regulate various biological processes by binding to the 3'-untranslated region of target gene mRNAs and suppressing their expression. Since abnormal expression patterns of miRNAs are a common feature in human malignancies, a number of them have been researched as potential therapeutic targets. Our previous study demonstrated that microRNA-18a (miR-18a) is upregulated in mesothelioma cell lines compared with in non-neoplastic mesothelial tissues, but its function remains unclear. In the present study, miRNA inhibitor was transfected into mesothelioma cell lines and then analyzed various cellular functions. Mesothelioma cells transfected with the miR-18a inhibitor exhibited lower proliferation and migration rates compared with cells transfected with a negative control inhibitor in proliferation and wound scratch assays, respectively. Additionally, the present study revealed that downregulation of miR-18a increased mesothelioma cell apoptosis. In a chemosensitivity assay, transfection of the miR-18a inhibitor significantly increased the sensitivity of mesothelioma cells to cisplatin but not to pemetrexed. Therefore, miR-18a may be a potential therapeutic target for mesothelioma resistant to cisplatin. Materials and methods Mesothelioma cell lines. Four human mesothelioma cell lines were used in this study. Two cell lines (ACC-MESO1 and ACC-MESO4) were purchased from the RIKEN BioResearch Center (Tsukuba, Japan) (15) and the other two (CRL-5915 and CRL-5946) were purchased from the American Type Culture Collection. Cells were cultured with Roswell Park Memorial

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MicroRNA miR‐125b can suppress ovarian granulosa cell functions: Interrelationships with FSH

Fabová

Loncová

Sirotkin

2022

Cell Biochemistry & Function

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This study aimed to evaluate the involvement of miR-125b and its interrelationship with follicle-stimulating hormone (FSH) in the control of basic ovarian granulosa cell functions. The effect of miR-125b mimics on basic functions of porcine ovarian granulosa cells cultured with and without FSH, and the effect of FSH on the expression of endogenous miR-125b was examined. Expression levels of miR-125b, viability, proliferation (accumulation of PCNA and cyclin B1), apoptosis (accumulation of bax and caspase 3), the accumulation of FSH receptors (FSHR), steroid hormones, insulin-like growth factor I (IGF-I), oxytocin, and prostaglandin E2 release were analysed by reverse transcription-quantitative polymerase chain reaction, Trypan blue exclusion test, quantitative immunocytochemistry, and ELISA. Transfection of cells with miR-125b mimics inhibited cell viability, proliferation, apoptosis, the occurrence of FSHR, progesterone, testosterone, estradiol, and oxytocin release but stimulated prostaglandin E2 output. FSH promoted cell viability, proliferation, steroid hormones, IGF-I, oxytocin, and prostaglandin E2 output and reduced the expression of miR-125b and apoptosis. Furthermore, miR-125b mimics supported the effect of FSH on the release of estradiol, IGF-I, and prostaglandin E2, and inverted FSH influence on cell viability, proliferation, apoptosis, progesterone, and testosterone output. FSH supported both inhibitory and stimulatory action of miR-125b on ovarian cell functions. Present observations indicate that: miR-125b can be involved in the control of basic ovarian functions and that miR-125b and FSH are antagonists in their actions on ovarian cell functions. The ability of FSH to reduce miR-125b expression and the ability of miR-125b mimics to decrease the occurrence of FSHR and to modify FSH effects indicate the existence of the self-inhibiting FSH-miR-125b axis and that miR-125b can mediate the actions of FSH on ovarian cells.

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MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

Cited by 105 publications

References 85 publications

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Inhibition of miR‑18a‑3p reduces proliferation of mesothelioma cells and sensitizes them to cisplatin

MicroRNA miR‐125b can suppress ovarian granulosa cell functions: Interrelationships with FSH

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