Circ_0061140 Knockdown Inhibits Tumorigenesis and Improves PTX Sensitivity by Regulating MiR-136/CBX2 Axis in Ovarian Cancer
Overview
Reproductive Medicine
Authors
Affiliations
Background: Ovarian cancer is an aggressive tumor in women with high mortality. Paclitaxel (PTX) can be used for the chemotherapy of ovarian cancer. Here, the roles of circular_0061140 (circ_0061140) in PTX sensitivity and malignant progression of ovarian cancer are unveiled.
Methods: The expressions of circ_0061140, microRNA-136 (miR-136) and chromobox 2 (CBX2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot. The half maximal inhibitory concentration (IC) of PTX was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was investigated by cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis was demonstrated by flow cytometry analysis. Cell migration and invasion were evaluated by transwell assay. The binding relationship between miR-136 and circ_0061140 or CBX2 was predicted by interactome or starbase online database, and identified by dual-luciferase reporter assay. The effects of circ_0061140 on tumor formation and PTX sensitivity in vivo were disclosed by tumor formation assay.
Results: Circ_0061140 and CBX2 expressions were upregulated, while miR-136 expression was downregulated in PTX-resistant tissues and cells compared with control groups. Circ_0061140 knockdown repressed cell proliferation, migration and invasion, and promoted cell apoptosis and PTX sensitivity; however, these effects were restrained by miR-136 RNAi. Additionally, circ_0061140 was a sponge of miR-136, and miR-136 bound to CBX2. Furthermore, circ_0061140 knockdown inhibited tumor formation and improved PTX sensitivity in vivo.
Conclusions: Circ_0061140 silencing repressed the progression and PTX resistance of ovarian cancer by downregulating CBX2 expression via sponging miR-136, which provided novel insight into studying the therapy of ovarian cancer with PTX.
Interplay of microRNAs and circRNAs in Epithelial Ovarian Cancer.
Schwarzenbach H Noncoding RNA. 2024; 10(5).
PMID: 39452837 PMC: 11510331. DOI: 10.3390/ncrna10050051.
USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2.
Chen J, Shan W, Jia Q, Chen Y, Jiang W, Tian Y Oncogene. 2024; 43(43):3170-3183.
PMID: 39256572 DOI: 10.1038/s41388-024-03151-9.
Wang J, Yang B, Wang Y, Liu S, Ma C, Piao J Front Pharmacol. 2024; 15:1430891.
PMID: 39114365 PMC: 11303140. DOI: 10.3389/fphar.2024.1430891.
Has_circ_0008285/miR-211-5p/SIRT-1 Axis Suppress Ovarian Cancer Cells Progression.
Elmizadeh K, Homaei A, Bahadoran E, Abbasi F, Moghbelinejad S Int J Mol Cell Med. 2024; 12(4):401-422.
PMID: 39006198 PMC: 11240052. DOI: 10.22088/IJMCM.BUMS.12.4.401.
Weidle U, Birzele F Cancer Genomics Proteomics. 2024; 21(3):213-237.
PMID: 38670587 PMC: 11059596. DOI: 10.21873/cgp.20442.