Silencing of miR-1246 Induces Cell Cycle Arrest and Apoptosis in Cisplatin-Resistant Ovarian Cancer Cells by Promoting ZNF23 Transcription

2021 ◽  
pp. 1-13
Author(s):  
Lu Cai ◽  
Qian Zhang ◽  
Lili Du ◽  
Feiyun Zheng
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Luciferase Reporter ◽  
Cycle Phase ◽  
Ovarian Cancer Cells ◽  
Tunel Staining ◽  
Cycle Arrest

Ovarian cancer (OC) is the most frequent cause of death among patients with gynecologic malignancies. In recent years, the development of cisplatin (DDP) resistance has become an important reason for the poor prognosis of OC patients. Therefore, it is vital to explore the mechanism of DDP resistance in OC. In this study, microRNA-1246 (miR-1246) expression in OC and DDP-resistant OC cells was determined by RT-qPCR, and chemosensitivity to DDP was assessed by the CCK-8 assay. A dual-luciferase reporter assay was performed to confirm the interaction between miR-1246 and zinc finger 23 (<i>ZNF23</i>), while changes in <i>ZNF23</i> expression were monitored by RT-qPCR, immunofluorescence, and western blot assays. Moreover, cell proliferation, cycle phase, and apoptosis were determined by EdU staining, flow cytometry, TUNEL staining, and Hoechst staining. Our data showed that miR-1246 was highly expressed in DDP-resistant OVCAR-3 and TOV-112D cells. Functionally, overexpression of miR-1246 markedly enhanced DDP resistance and cell proliferation, and suppressed cell cycle arrest and apoptosis of OC cells. Inhibition of miR-1246 expression significantly attenuated DDP resistance and cell proliferation, and increased cell cycle arrest and apoptosis in DDP-resistant OC cells. Furthermore, <i>ZNF23</i> was identified as a target gene of miR-1246, and ZNF23 protein expression was notably downregulated in DDP-resistant OC cells. Moreover, overexpression of miR-1246 significantly downregulated the <i>ZNF23</i> levels in OVCAR-3 and TOV-112D cells, and inhibition of miR-1246 upregulated the <i>ZNF23</i> levels in the DDP-resistant OVCAR-3 and TOV-112D cells. In conclusion, miR-1246 might be a novel regulator of DDP-resistant OC that functions by regulating <i>ZNF23</i> expression in DDP-resistant cells, as well as cell proliferation, cell cycle progression, and apoptosis.

Abstract 4087: ALDH1A1 inhibitor induces cell cycle arrest and reduces cell proliferation of cisplatin-resistant ovarian cancer cells

2020 ◽  
Author(s):  
Ilangovan Ramachandran ◽  
Sivakumar Ramadoss ◽  
Selvendiran Karuppaiyah ◽  
Lauren Nathan ◽  
R. Ileng Kumaran ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

scholarly journals miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chenyang Li ◽  
Yue Wang ◽  
Hao Wang ◽  
Bowen Wang ◽  
Yunxia Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cell Cycle Progression ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Skov3 Cell ◽  
Cycle Progression ◽  
Skov3 Cells

Objective. To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells. Methods. The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression. Results. miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression. Conclusion. Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.

scholarly journals Hyperbaric oxygen promotes not only glioblastoma proliferation but also chemosensitization by inhibiting HIF1α/HIF2α-Sox2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pan Wang ◽  
Sheng Gong ◽  
Jinyu Pan ◽  
Junwei Wang ◽  
Dewei Zou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Hyperbaric Oxygen ◽  
Cell Cycle Progression ◽  
Malignant Progression ◽  
Cycle Progression ◽  
Chemotherapy Sensitivity ◽  
Hypoxic Conditions ◽  
Cycle Arrest

AbstractThere exists a consensus that combining hyperbaric oxygen (HBO) and chemotherapy promotes chemotherapy sensitivity in GBM cells. However, few studies have explored the mechanism involved. HIF1α and HIF2α are the two main molecules that contribute to GBM malignant progression by inhibiting apoptosis or maintaining stemness under hypoxic conditions. Moreover, Sox2, a marker of stemness, also contributes to GBM malignant progression through stemness maintenance or cell cycle arrest. Briefly, HIF1α, HIF2α and Sox2 are highly expressed under hypoxia and contribute to GBM growth and chemoresistance. However, after exposure to HBO for GBM, whether the expression of the above factors is decreased, resulting in chemosensitization, remains unknown. Therefore, we performed a series of studies and determined that the expression of HIF1α, HIF2α and Sox2 was decreased after HBO and that HBO promoted GBM cell proliferation through cell cycle progression, albeit with a decrease in stemness, thus contributing to chemosensitization via the inhibition of HIF1α/HIF2α-Sox2.

scholarly journals Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

2010 ◽  
Vol 9 (1) ◽  
pp. 47 ◽  
Author(s):  
Christopher S Bryant ◽  
Sanjeev Kumar ◽  
Sreedhar Chamala ◽  
Jay Shah ◽  
Jagannath Pal ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cycle Arrest

scholarly journals Roquin1 Suppresses Breast Cancer Growth by Inducing Cell Cycle Arrest via Selectively Destabilizing Cell Cycle–Promoting Gene mRNAs

2020 ◽  
Author(s):  
Wenbao Lu ◽  
Meicen Zhou ◽  
Bing Wang ◽  
Xueting Liu ◽  
Bingwei Li
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Cycle Arrest

Abstract Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.

CA 125 Production and Release by Ovarian Cancer Cells In Vitro

1998 ◽  
Vol 13 (4) ◽  
pp. 200-206 ◽  
Author(s):  
E.P. Beck ◽  
A. Moldenhauer ◽  
E. Merkle ◽  
F. Kiesewetter ◽  
W. Jäger ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Human Tumor ◽  
Cellular Growth ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Cell Cycle Distribution ◽  
Cycle Arrest

The antigenic determinant CA 125 is a high molecular weight glycoprotein which is elevated in more than 80% of patients with epithelial ovarian cancer. Despite its good performance as a human tumor marker, only little is known about its physiological function. According to recent publications, CA 125 production and release appear to be related to cellular growth. In order to investigate this putative relationship more closely, we analyzed the pattern of CA 125 production and release by ovarian cancer cells during exponential cell growth, during cell cycle arrest by colchicine and during inhibition of cellular protein synthesis by cycloheximide. The results were correlated with the cell cycle distribution. According to our results, the main determinant of CA 125 release into the culture supernatant is the total cell count. Although cell cycle arrest in the G2 + M phase by means of colchicine treatment resulted in the death of most cells, which was reflected by an increased release of CA 125, no differences in the intracellular production rate between colchicine treated and untreated cells were seen. In contrast, treatment of cells with cycloheximide not only resulted in decreasing cell numbers but also in a complete inhibition of CA 125 production by surviving cells.

Sign in / Sign up

Export Citation Format

Share Document