Construction of <scp>miRNA‐lncRNA‐mRNA</scp> co‐expression network affecting <scp>EMT‐</scp>mediated cisplatin resistance in ovarian cancer

Naghsh-Nilchi, Amirhosein; Ghahnavieh, Laleh Ebrahimi; Dehghanian, Fariba

doi:10.1111/jcmm.17477

Cited by 8 publications

(5 citation statements)

References 127 publications

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“…Epithelial mesenchymal transition plays an important role in the progression of ovarian cancer and promotes chemotherapy resistance [15] . Epithelial mesenchymal transition refers to a reversible process in which relatively stable epithelial cells lose cell polarity and intercellular adhesion, and transform into spindle shaped stromal cells with migratory ability.…”

Section: Discussionmentioning

confidence: 99%

SDHB reduces chemotherapy resistance in ovarian cancer cells by affecting epithelial mesenchymal transition through DNA damage repair

Chen,

2024

Preprint

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Background: Ovarian carcinoma is one of the most common gynecological cancers with high mortality rates. Succinate dehydrogenase (SDH or Complex II) which is one of the important enzymes in the tricarboxylic acid (TCA) cycle plays an important role in carcinomas. Succinate dehydrogenase subunit B (SDHB) gene, which encodes one of the four subunits of SDH, has been found played as a tumor suppressor role in ovarian cancer. However, the role of SDHB in ovarian cancer chemotherapy is still unclear. Methods: Using the SDHB specific siRNA and overexpression plasmid, the expression of SDHB was silenced and conversely induced in ovarian cancer cell lines SKOV3 and A2780, respectively. The possible role of SDHB in ovarian cancer chemotherapy was investigated in vitro using CCK8 and Colony formation assays. Real-time PCR was used to exam the expression of SDH subunits in ovarian cancer tissues and normal ovarian tissues. Immunohistochemistry was used to exam the expression of SDHB in human ovarian cancer cisplatin-resistant tissues and corresponding cisplatin-sensitive tissues. To explore the mechanism, epithelial mesenchymal transition (EMT) and DNA damage repair related proteins such as E-cadherin, Vimentin, γ-H2AX and ERCC1 were examined by western blot in SKOV3 and A2780 cells. EMT related transcription factors such as Slug, Snail and Twist mRNA levels were examined by quantitative real-time reverse transcriptase PCR. Results: Succinate dehydrogenase subunits were expressed lower in ovarian cancer tissues than in normal ovarian tissues, with the SDHB subunit being expressed lower in ovarian cancer tissues. Moreover, the expression of SDHB in ovarian cancer metastatic tissues was lower than that in primary tissues, and SDHB expressed lower in human ovarian cancer cisplatin-resistant tissues than the corresponding cisplatin-sensitive tissues. In SDHB silenced ovarian cancer cells, E-cadherin was decreased, Vimentin was increased. The EMT- related transcription factors Snail and Slug were significantly increased (P<0.05), while Twist showed no significant increase (P>0.05) in SDHB-silenced cancer cells. In contrast, overexpression of SDHB increased E-cadherin expression and reduced Vimentin expression in SKOV3 cells. SDHB silencing increased drug resistance and SDHB overexpression showed the opposite results in SKOV3 and A2780 cells. In SDHB-silenced cancer cells, the level of ERCC1, which contributes to platinum drug resistance by promoting DNA repair, was increased, and γ-H2AX, which is related to cell apoptosis and drug resistance was decreased, and SDHB overexpression showed the opposite results in SKOV3 cells. Conclusions: SDHB reduced the chemotherapy resistance of ovarian cancer cells significantly, and its mechanism might be by inhibiting epithelial mesenchymal transition of ovarian cancer cells, further reducing their DNA damage repair ability and thereby reducing chemotherapy resistance, which provides a preliminary experimental and theoretical basis for the treatment of ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

SDHB reduces chemotherapy resistance in ovarian cancer cells by affecting epithelial mesenchymal transition through DNA damage repair

Chen,

2024

Preprint

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“…EMT is involved in many changes in the cellular environment during cancer treatment, for example, changes in cell phenotype, loss of cell polarity, and remodeling of the extracellular matrix. These changes are also core factors for the emergence of drug resistance [ 13 ]. EMT-related markers also play a key role in the formation of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1

Wang

et al. 2023

Anti-Cancer Drugs

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Adenosine deaminases acting on RNA1 (ADAR1) are involved in the occurrence and development of cancers. Although the role of ADAR1 in gastric cancer metastasis has been reported, the role of ADAR1 in the mechanism of cisplatin resistance in gastric cancer is not clear. In this study, human gastric cancer tissue specimens were used to construct cisplatin-resistant gastric cancer cells; the results indicated that the mechanism underlying the inhibition of gastric cancer metastasis and reversal of cisplatin-resistant gastric cancer by ADAR1 inhibits gastric cancer occurs through the antizyme inhibitor 1 (AZIN1) pathway. We assessed ADAR1 and AZIN1 expression in the tissues of patients with low to moderately differentiated gastric cancer. Gastric cancer cells (human gastric adenocarcinoma cell line [AGS] and HGC-27 cells) and gastric cancer cisplatin-resistant cells (AGSCDDP and HGC-27CDDP) were selected, and the protein expression of ADAR1 and AZIN1 was detected using immunocytochemistry and immunocytofluorescence. The effects of ADAR1 small interfering RNA (siRNA) on the invasion, migration and proliferation of cisplatin-resistant gastric cancer cells were investigated. Western blot assays were used to assess the protein expression levels of ADAR1, AZIN1 and epithelial–mesenchymal transition (EMT)-related markers. In-vivo experiments, a subcutaneous tumor formation model of nude mice was established, and the effects of ADAR1 on tumor growth and AZIN1 expression level were detected by hematoxylin and eosin, immunohistochemistry and western blot. The expression of ADAR1 and AZIN1 in human gastric cancer tissue was significantly higher than that in paracancerous tissues. The colocalization of ADAR1, AZIN1 and E-cadherin expression in immunofluorescence assays indicated a significant correlation between the three. In in-vitro experiments, ADAR1 knockout not only reduced the invasion and migration ability of AGS and HGC-27 cells but also reduced that of cisplatin-resistant gastric cancer cells. ADAR1 siRNA inhibited the proliferation and decreased the colony number of cisplatin-resistant gastric cancer cells. ADAR1 siRNA decreased the expression of AZIN1 and EMT-related marker proteins (vimentin, N-cadherin, β-catenin, MMP9, MMP2 and TWIST). The effect of ADAR1 siRNA combined with AZIN1 siRNA was more significant. In-vivo, the knockdown of ADAR1 significantly inhibited tumor growth and AZIN1 expression. ADAR1 and AZIN1 are antimetastatic targets of gastric cancer, and AZIN1 is a downstream regulatory target of ADAR1. ADAR1 knockout can inhibit the metastasis of gastric cancer cells and reverse the cisplatin resistance of gastric cancer cells by downregulating the expression of AZIN1, potentially resulting in increased treatment efficacy.

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“…S refers to the single residue pair match scores of the matching area, and ΔG refers to the free energy of double chain binding [ 23 ]. Then, the miRNAs, lncRNAs and mRNAs were used to construct a ceRNA regulatory network of lncRNAs‒miRNAs‒mRNAs using Cytoscape software [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Identification of a hippocampal lncRNA-regulating network in a natural aging rat model

Liu

et al. 2022

BMC Neurosci

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Background Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed. Results A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM—receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA–miRNA–mRNA target pairs were confirmed in this lncRNA‒miRNA‒mRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs. Conclusions We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.

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Construction of miRNA‐lncRNA‐mRNA co‐expression network affecting EMT‐mediated cisplatin resistance in ovarian cancer

Cited by 8 publications

References 127 publications

SDHB reduces chemotherapy resistance in ovarian cancer cells by affecting epithelial mesenchymal transition through DNA damage repair

SDHB reduces chemotherapy resistance in ovarian cancer cells by affecting epithelial mesenchymal transition through DNA damage repair

ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1

Identification of a hippocampal lncRNA-regulating network in a natural aging rat model

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