Abstract
Introduction: Circular RNAs (circRNAs) are important biological molecules associated with the pathogenesis of multiple cancers.
Objective: This work aimed to investigate the function and molecular mechanism of circ_0070203 in high-grade serous ovarian cystadenocarcinoma (HGSOC).
Methods: circRNA microarray was conducted to detect the circ_0070203 expression in HGSOC tissues. Bioinformatics analysis was used to find the binding sites between circ_0070203, miR- 370-3p and TGFβR2. Real-time quantitative reverse transcription PCR (RT-qPCR) was executed to detect the expressions of circ_0070203, miR-370-3p and TGFβR2 in HGSOC tissues and SKOV3 cells. Dual-luciferase reporter gene assay was used to validate the relationships between miR-370-3p and circ_0070203 or TGFβR2. Besides, transwell assays were conducted to assess the migrative, invasive abilities of ovarian cancer (OC) cells. Western blotting was adopted to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. The related patents were also studied during the research.
Results: Circ_0070203 and TGFβR2 were upregulated, while miR-370-3p was downregulated in FIGO stage III-IV HGSOC tissues and SKOV-3 cell lines. circ_0070203 overexpression changed the expression of other EMT-related proteins and enhanced the migrative, invasive abilities of OC cells, while silencing circ_0070203 worked oppositely. Mechanistically, circ_0070203 could upregulate TGFβR2 expression in OC cells via sponging miR-370-3p.
Conclusion: Circ_0070203 could promote the epithelial-mesenchymal transition, invasion, and metastasis of HGSOC via regulating the miR-370-3p/TGFβR2 axis. Our findings provided a potential biomarker for HGSOC therapy.
[http://dx.doi.org/10.1016/S0140-6736(09)61338-6] [PMID: 19793610]
[http://dx.doi.org/10.1038/nrc2946] [PMID: 20944665]
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[http://dx.doi.org/10.5603/GP.a2017.0098] [PMID: 29192414]
[http://dx.doi.org/10.1016/j.canlet.2011.12.036] [PMID: 22245949]
[http://dx.doi.org/10.1038/nrm3758] [PMID: 24556840]
[http://dx.doi.org/10.1038/s41580-018-0080-4] [PMID: 30459476]
[http://dx.doi.org/10.1038/cddis.2016.149] [PMID: 27277676]
[http://dx.doi.org/10.1186/s13046-019-1061-y] [PMID: 30819230]
[http://dx.doi.org/10.1186/s12943-018-0870-5] [PMID: 30098599]
[http://dx.doi.org/10.1038/s41580-020-0243-y] [PMID: 32366901]
[http://dx.doi.org/10.3389/fonc.2019.01105] [PMID: 31750237]
[http://dx.doi.org/10.3748/wjg.v23.i34.6330] [PMID: 28974900]
[http://dx.doi.org/10.1186/s12943-018-0936-4] [PMID: 30674324]
[http://dx.doi.org/10.1186/s12935-020-01420-7] [PMID: 32714095]
[PMID: 32495861]
[http://dx.doi.org/10.2147/CMAR.S291218] [PMID: 33732019]
[http://dx.doi.org/10.1186/s12943-018-0889-7] [PMID: 30261900]
[http://dx.doi.org/10.1186/s12943-019-1071-6] [PMID: 31526370]
[http://dx.doi.org/10.7150/jca.35041] [PMID: 31942183]
[http://dx.doi.org/10.1080/15384101.2021.1965723] [PMID: 34465271]
[http://dx.doi.org/10.1038/s41467-018-06434-4] [PMID: 30333487]
[http://dx.doi.org/10.3748/wjg.v20.i30.10432] [PMID: 25132759]
[http://dx.doi.org/10.1016/j.mam.2018.07.003] [PMID: 30102929]
[http://dx.doi.org/10.1007/s43032-021-00717-w] [PMID: 34973152]
[PMID: 27249599]
[http://dx.doi.org/10.1016/j.biopha.2013.04.014] [PMID: 23721824]
[http://dx.doi.org/10.1007/s12282-017-0793-9] [PMID: 28721656]
[http://dx.doi.org/10.1007/s10585-021-10077-z] [PMID: 33590419]
[http://dx.doi.org/10.1016/j.ygeno.2019.05.002] [PMID: 31071459]
[http://dx.doi.org/10.1007/s00441-014-1953-2] [PMID: 25124796]
(b) Xie D. Medicament for targeted therapy of ovarian cancer and preparation method of medicament. CN10755093 0A, 2018.;
c) Burger RA. Combination therapy of carboplatin and NAPI2B-targeted polymer antibody-drug conjugate for the treatment of ovarian cancer. WO2022235636A1, 2022.
[http://dx.doi.org/10.1016/j.bpobgyn.2016.12.001] [PMID: 28111228]
[http://dx.doi.org/10.1002/1878-0261.12371] [PMID: 30107086]
[http://dx.doi.org/10.18632/aging.103668] [PMID: 32877369]
[http://dx.doi.org/10.1186/s10020-020-00194-y] [PMID: 32640974]
[http://dx.doi.org/10.1038/s41419-022-04646-7] [PMID: 35236825]
[http://dx.doi.org/10.1093/carcin/bgr246] [PMID: 22072622]
[http://dx.doi.org/10.1016/j.ymthe.2019.02.002] [PMID: 30879950]
[http://dx.doi.org/10.1016/j.chemosphere.2018.12.016] [PMID: 30543962]
[http://dx.doi.org/10.1186/1476-4598-13-51] [PMID: 24606633]
[http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]
[http://dx.doi.org/10.1038/nature11956] [PMID: 23446351]
(b) Zhou Z, Xiao J, Zhang W, et al. Osteosarcoma biomarker circular RNAcirc_0006633 and application thereof. CN109762897A, 2019.
[http://dx.doi.org/10.3389/fonc.2020.545460] [PMID: 33312941]