&lt;p&gt;LncRNA MALAT1 Promotes Survival of Epithelial Ovarian Cancer Cells by Downregulating miR-145-5p&lt;/p&gt;

Wang, Ke; Zhao, Ye; Wang, Yimin

doi:10.2147/cmar.s267355

Cited by 12 publications

(7 citation statements)

References 27 publications

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“…MALAT1, a nuclear-restricted housekeeping regulatory lncRNA located on chromosome 11q13, was reported to be overexpressed across various human carcinoma types. Once downregulated, MALAT1 effectively leads to the suppression of tumor cell survival, proliferation, the EMT, and cell migration [ 4 , 5 , 6 ]. Epithelial ovarian cancer (OC; EOC) is one of the lethal gynecological cancers, with evidence that lncRNAs participate in tumorigenesis [ 7 ] and genetic regulatory functions [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA MALAT1 Facilitates Ovarian Cancer Progression through Promoting Chemoresistance and Invasiveness in the Tumor Microenvironment

Mao

Fan

Dlamini

et al. 2021

IJMS

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Upregulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1, also known as nuclear-enriched abundant transcript 2 (NEAT2) or LINC00047) was found in various solid tumors, including epithelial ovarian cancer (EOC). MALAT1 is a long noncoding (lnc)RNA that regulates many functional signaling pathways, including tumorigenesis. Herein, we observed the consistent upregulation of MALAT1 in MYST4-overexpressing cell lines, while MALAT1 was frequently found to be upregulated in various types of clinical carcinoma tissues, especially EOC. To further investigate the lncRNA MALAT1 in EOC progression, the transduced overexpression of MALAT1 in EOC cell lines and cancer-associated fibroblasts (CAFs) was employed. We found that MALAT1 overexpression in EOC cell lines significantly increased drug resistance, cell migration, and invasion. Furthermore, the concomitant overexpression of MALAT1 in EOC cells and CAFs dramatically increased EOC cell invasion. Accordingly, a mechanistic investigation of MALAT1 overexpression in EOC cells showed that expressions of the cytokines interleukin (IL)-1β and p-P38/p-NFκB/Cox2/prostaglandin E2 (PGE2) signaling were significantly increased, which stimulated inflammatory responses, whereas cell apoptosis was inhibited due to increased Bcl-2 levels and reduced Caspase3 levels. After MALAT1 was overexpressed in EOC cells, and the cyclin D1, p-PI3K, and p-Akt expressions increased, suggesting the promotion of tumor cell proliferation, while increased zinc finger E-box-binding homeobox-2 (ZEB2), yes-associated protein (YAP), and vimentin expression with E-cadherin downregulation indicated the enhancement of the epithelial-to-mesenchymal transition (EMT) in terms of metastasis, thereby triggering EOC progression. Together, our findings demonstrate how MALAT1 overexpression facilitates an oncogenic function through inhibiting tumor cell apoptosis, combined with increasing tumor cell inflammation, proliferation, and invasion in the EOC tumor microenvironment. MALAT1 is thus a potential diagnostic marker and therapeutic for this malignancy.

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Section: Introductionmentioning

confidence: 99%

LncRNA MALAT1 Facilitates Ovarian Cancer Progression through Promoting Chemoresistance and Invasiveness in the Tumor Microenvironment

Mao

Fan

Dlamini

et al. 2021

IJMS

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“…It enhances cell motility of lung adenocarcinoma cells through regulating the motility-related genes such as collagen triple helix repeat containing 1 (CTHRC1), chaperonin-containing tailless complex polypeptide, subunit 4 (CCT4), hyualuronan-mediated motility receptor (HMMR), and regulator of differentiation 1 (ROD1) via transcriptional and/or post-transcriptional regulation [120]. It also promotes epithelial ovarian cancer cell survival and progression by acting as a sponge for miRNAs [121]. It acts as a sponge for miR-22 and counteracts its inhibitory effect on c-myc-mediated epithelial-mesenchymal transition [122].…”

Section: Long Non-coding Rnas and Cancermentioning

confidence: 99%

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

et al. 2022

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Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.

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“…OV is the second most frequent malignancy in women’s health and the leading cause of mortality from gynecological cancers [ 1 – 6 ]. About 70% of patients with OV are not detected until late stages because of a lack of early symptoms, indicators, and effective screening tools [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer

et al. 2023

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Objective Ovarian cancer (OV) has a high mortality rate all over the world, and extrachromosomal circular DNA (eccDNA) plays a key role in carcinogenesis. We wish to study more about the molecular structure of eccDNA in the UACC-1598–4 cell line and how its genes are associated with ovarian cancer prognosis. Methods We sequenced and annotated the eccDNA by Circle_seq of the OV cell line UACC-1598–4. To acquire the amplified genes of OV on eccDNA, the annotated eccDNA genes were intersected with the overexpression genes of OV in TCGA. Univariate Cox regression was used to find the genes on eccDNA that were linked to OV prognosis. The least absolute shrinkage and selection operator (LASSO) and cox regression models were used to create the OV prognostic model, as well as the receiver operating characteristic curve (ROC) curve and nomogram of the prediction model. By applying the median value of the risk score, the samples were separated into high-risk and low-risk groups, and the differences in immune infiltration between the two groups were examined using ssGSEA. Results EccDNA in UACC-1598–4 has a length of 0-2000 bp, and some of them include the whole genes or gene fragments. These eccDNA originated from various parts of chromosomes, especially enriched in repeatmasker, introns, and coding regions. They were annotated with 2188 genes by Circle_seq. Notably, the TCGA database revealed that a total of 198 of these eccDNA genes were overexpressed in OV (p < 0.05). They were mostly enriched in pathways associated with cell adhesion, ECM receptors, and actin cytoskeleton. Univariate Cox analysis showed 13 genes associated with OV prognosis. LASSO and Cox regression analysis were used to create a risk model based on remained 9 genes. In both the training (TCGA database) and validation (International Cancer Genome Consortium, ICGC) cohorts, a 9-gene signature could successfully discriminate high-risk individuals (all p < 0.01). Immune infiltration differed significantly between the high-risk and low-risk groups. The model’s area under the ROC curve was 0.67, and a nomograph was created to assist clinician. Conclusion EccDNA is found in UACC-1598–4, and part of its genes linked to OV prognosis. Patients with OV may be efficiently evaluated using a prognostic model based on eccDNA genes, including SLC7A1, NTN1, ADORA1, PADI2, SULT2B1, LINC00665, CILP2, EFNA5, TOMM.

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<p>LncRNA MALAT1 Promotes Survival of Epithelial Ovarian Cancer Cells by Downregulating miR-145-5p</p>

Cited by 12 publications

References 27 publications

LncRNA MALAT1 Facilitates Ovarian Cancer Progression through Promoting Chemoresistance and Invasiveness in the Tumor Microenvironment

LncRNA MALAT1 Facilitates Ovarian Cancer Progression through Promoting Chemoresistance and Invasiveness in the Tumor Microenvironment

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

A novel extrachromosomal circular DNA related genes signature for overall survival prediction in patients with ovarian cancer

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