Skip to main content
Top
Published in: Cancer Cell International 1/2020

01-12-2020 | Ovarian Cancer | Primary research

Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis

Authors: Wumei Lin, Haiyan Ye, Keli You, Le Chen

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

Ovarian cancer (OC) is a common fatal malignant tumor of female reproductive system worldwide. Growing studies have proofed that circular RNAs (circRNAs) engage in the regulation of various types of cancers. However, the underlying biological functions and effect mechanism of circular RNA_LARP4 (circ_LARP4) in OC have not been explored.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect the expression of circ_LARP4 in OC cells. The function of circ_LARP4 was measured by cell counting kit-8 (CCK-8), colony formation assay and transwell assay. RNA immunoprecipitation (RIP) assay and luciferase reporter assays assessed the binding correlation between miR-513b-5p and circ_LARP4 (or LARP4).

Results

The expression of circ_LARP4 in OC cells was much lower than that in human normal ovarian epithelial cells. Overexpressing circ_LARP4 impaired cell proliferation, invasion and migration abilities. Circ_LARP4 worked as a competing endogenous RNA (ceRNA) to sponge miR-513b-5p. Furthermore, LARP4 was indirectly modulated by circ_LARP4 as the downstream target of miR-513b-5p, as well as the host gene of circ_LARP4.

Conclusion

Circ_LARP4 could hamper cell proliferation and migration by sponging miR-513b-5p to regulate the expression of LARP4. This research may provide some referential value to OC treatment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bookman MA. Optimal primary therapy of ovarian cancer. Ann Oncol. 2016;27(Suppl 1):i58–62.CrossRef Bookman MA. Optimal primary therapy of ovarian cancer. Ann Oncol. 2016;27(Suppl 1):i58–62.CrossRef
2.
go back to reference Yokoi A, Matsuzaki J, Yamamoto Y, Yoneoka Y, Takahashi K, Shimizu H, Uehara T, Ishikawa M, Ikeda SI, Sonoda T, et al. Integrated extracellular microRNA profiling for ovarian cancer screening. Nat Commun. 2018;9(1):4319.CrossRef Yokoi A, Matsuzaki J, Yamamoto Y, Yoneoka Y, Takahashi K, Shimizu H, Uehara T, Ishikawa M, Ikeda SI, Sonoda T, et al. Integrated extracellular microRNA profiling for ovarian cancer screening. Nat Commun. 2018;9(1):4319.CrossRef
3.
go back to reference Pisanic TR 2nd, Cope LM, Lin SF, Yen TT, Athamanolap P, Asaka R, Nakayama K, Fader AN, Wang TH, Shih IM, et al. Methylomic analysis of ovarian cancers identifies tumor-specific alterations readily detectable in early precursor lesions. Clin Cancer Res. 2018;24(24):6536–47.CrossRef Pisanic TR 2nd, Cope LM, Lin SF, Yen TT, Athamanolap P, Asaka R, Nakayama K, Fader AN, Wang TH, Shih IM, et al. Methylomic analysis of ovarian cancers identifies tumor-specific alterations readily detectable in early precursor lesions. Clin Cancer Res. 2018;24(24):6536–47.CrossRef
4.
go back to reference Zheng M, Hu Y, Gou R, Wang J, Nie X, Li X, Liu Q, Liu J, Lin B. Integrated multi-omics analysis of genomics, epigenomics, and transcriptomics in ovarian carcinoma. Aging. 2019;11(12):4198–215.CrossRef Zheng M, Hu Y, Gou R, Wang J, Nie X, Li X, Liu Q, Liu J, Lin B. Integrated multi-omics analysis of genomics, epigenomics, and transcriptomics in ovarian carcinoma. Aging. 2019;11(12):4198–215.CrossRef
5.
go back to reference Kim JH, Park CW, Um D, Baek KH, Jo Y, An H, Kim Y, Kim TJ. Mass spectrometric screening of ovarian cancer with serum glycans. Dis Markers. 2014;2014:634289.CrossRef Kim JH, Park CW, Um D, Baek KH, Jo Y, An H, Kim Y, Kim TJ. Mass spectrometric screening of ovarian cancer with serum glycans. Dis Markers. 2014;2014:634289.CrossRef
6.
go back to reference Heindl A, Khan AM, Rodrigues DN, Eason K, Sadanandam A, Orbegoso C, Punta M, Sottoriva A, Lise S, Banerjee S, et al. Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity. Nat Commun. 2018;9(1):3917.CrossRef Heindl A, Khan AM, Rodrigues DN, Eason K, Sadanandam A, Orbegoso C, Punta M, Sottoriva A, Lise S, Banerjee S, et al. Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity. Nat Commun. 2018;9(1):3917.CrossRef
7.
go back to reference Blyuss O, Burnell M, Ryan A, Gentry-Maharaj A, Marino IP, Kalsi J, Manchanda R, Timms JF, Parmar M, Skates SJ, et al. Comparison of longitudinal CA125 algorithms as a first-line screen for ovarian cancer in the general population. Clin Cancer Res. 2018;24(19):4726–33.CrossRef Blyuss O, Burnell M, Ryan A, Gentry-Maharaj A, Marino IP, Kalsi J, Manchanda R, Timms JF, Parmar M, Skates SJ, et al. Comparison of longitudinal CA125 algorithms as a first-line screen for ovarian cancer in the general population. Clin Cancer Res. 2018;24(19):4726–33.CrossRef
8.
go back to reference Yang W, Gu J, Wang X, Wang Y, Feng M, Zhou D, Guo J, Zhou M. Inhibition of circular RNA CDR1as increases chemosensitivity of 5-FU-resistant BC cells through up-regulating miR-7. J Cell Mol Med. 2019;23(5):3166–77.CrossRef Yang W, Gu J, Wang X, Wang Y, Feng M, Zhou D, Guo J, Zhou M. Inhibition of circular RNA CDR1as increases chemosensitivity of 5-FU-resistant BC cells through up-regulating miR-7. J Cell Mol Med. 2019;23(5):3166–77.CrossRef
9.
go back to reference Zhang H, Wang G, Ding C, Liu P, Wang R, Ding W, Tong D, Wu D, Li C, Wei Q, et al. Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression. Oncotarget. 2017;8(37):61687–97.PubMedPubMedCentral Zhang H, Wang G, Ding C, Liu P, Wang R, Ding W, Tong D, Wu D, Li C, Wei Q, et al. Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression. Oncotarget. 2017;8(37):61687–97.PubMedPubMedCentral
10.
go back to reference Zhong Z, Huang M, Lv M, He Y, Duan C, Zhang L, Chen J. Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway. Cancer Lett. 2017;403:305–17.CrossRef Zhong Z, Huang M, Lv M, He Y, Duan C, Zhang L, Chen J. Circular RNA MYLK as a competing endogenous RNA promotes bladder cancer progression through modulating VEGFA/VEGFR2 signaling pathway. Cancer Lett. 2017;403:305–17.CrossRef
11.
go back to reference Qu S, Zhong Y, Shang R, Zhang X, Song W, Kjems J, Li H. The emerging landscape of circular RNA in life processes. RNA Biol. 2017;14(8):992–9.CrossRef Qu S, Zhong Y, Shang R, Zhang X, Song W, Kjems J, Li H. The emerging landscape of circular RNA in life processes. RNA Biol. 2017;14(8):992–9.CrossRef
12.
go back to reference Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H. Circular RNA: a new star of noncoding RNAs. Cancer Lett. 2015;365(2):141–8.CrossRef Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H. Circular RNA: a new star of noncoding RNAs. Cancer Lett. 2015;365(2):141–8.CrossRef
13.
go back to reference Hansen TB, Kjems J, Damgaard CK. Circular RNA and miR-7 in cancer. Cancer Res. 2013;73(18):5609–12.CrossRef Hansen TB, Kjems J, Damgaard CK. Circular RNA and miR-7 in cancer. Cancer Res. 2013;73(18):5609–12.CrossRef
14.
go back to reference Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.CrossRef Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, Luo Y, Lyu D, Li Y, Shi G, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.CrossRef
15.
go back to reference Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X, Zhu J. Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer. 2017;16(1):151.CrossRef Zhang J, Liu H, Hou L, Wang G, Zhang R, Huang Y, Chen X, Zhu J. Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression. Mol Cancer. 2017;16(1):151.CrossRef
16.
go back to reference Zou T, Wang PL, Gao Y, Liang WT. Circular RNA_LARP4 is lower expressed and serves as a potential biomarker of ovarian cancer prognosis. Eur Rev Med Pharmacol Sci. 2018;22(21):7178–82.PubMed Zou T, Wang PL, Gao Y, Liang WT. Circular RNA_LARP4 is lower expressed and serves as a potential biomarker of ovarian cancer prognosis. Eur Rev Med Pharmacol Sci. 2018;22(21):7178–82.PubMed
17.
go back to reference Bai X, Zhou Y, Ouyang N, Liu L, Huang X, Tian J, Lv T. A de novo mutation in the MTUS1 gene decreases the risk of non-compaction of ventricular myocardium via the Rac1/Cdc42 pathway. Front Pediatr. 2019;7:247.CrossRef Bai X, Zhou Y, Ouyang N, Liu L, Huang X, Tian J, Lv T. A de novo mutation in the MTUS1 gene decreases the risk of non-compaction of ventricular myocardium via the Rac1/Cdc42 pathway. Front Pediatr. 2019;7:247.CrossRef
18.
go back to reference Merret R, Martino L, Bousquet-Antonelli C, Fneich S, Descombin J, Billey E, Conte MR, Deragon JM. The association of a La module with the PABP-interacting motif PAM2 is a recurrent evolutionary process that led to the neofunctionalization of La-related proteins. RNA (New York, NY). 2013;19(1):36–50.CrossRef Merret R, Martino L, Bousquet-Antonelli C, Fneich S, Descombin J, Billey E, Conte MR, Deragon JM. The association of a La module with the PABP-interacting motif PAM2 is a recurrent evolutionary process that led to the neofunctionalization of La-related proteins. RNA (New York, NY). 2013;19(1):36–50.CrossRef
19.
go back to reference Yang R, Gaidamakov SA, Xie J, Lee J, Martino L, Kozlov G, Crawford AK, Russo AN, Conte MR, Gehring K, et al. La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability. Mol Cell Biol. 2011;31(3):542–56.CrossRef Yang R, Gaidamakov SA, Xie J, Lee J, Martino L, Kozlov G, Crawford AK, Russo AN, Conte MR, Gehring K, et al. La-related protein 4 binds poly(A), interacts with the poly(A)-binding protein MLLE domain via a variant PAM2w motif, and can promote mRNA stability. Mol Cell Biol. 2011;31(3):542–56.CrossRef
20.
go back to reference Gandin V, Senft D, Topisirovic I, Ronai ZA. RACK1 function in cell motility and protein synthesis. Genes Cancer. 2013;4(9–10):369–77.CrossRef Gandin V, Senft D, Topisirovic I, Ronai ZA. RACK1 function in cell motility and protein synthesis. Genes Cancer. 2013;4(9–10):369–77.CrossRef
21.
go back to reference Zhong Z, Lv M, Chen J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 2016;6:30919.CrossRef Zhong Z, Lv M, Chen J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 2016;6:30919.CrossRef
22.
go back to reference Xie H, Ren X, Xin S, Lan X, Lu G, Lin Y, Yang S, Zeng Z, Liao W, Ding YQ, et al. Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer. Oncotarget. 2016;7(18):26680–91.PubMedPubMedCentral Xie H, Ren X, Xin S, Lan X, Lu G, Lin Y, Yang S, Zeng Z, Liao W, Ding YQ, et al. Emerging roles of circRNA_001569 targeting miR-145 in the proliferation and invasion of colorectal cancer. Oncotarget. 2016;7(18):26680–91.PubMedPubMedCentral
23.
go back to reference Taborda MI, Ramirez S, Bernal G. Circular RNAs in colorectal cancer: possible roles in regulation of cancer cells. World J Gastrointest Oncol. 2017;9(2):62–9.CrossRef Taborda MI, Ramirez S, Bernal G. Circular RNAs in colorectal cancer: possible roles in regulation of cancer cells. World J Gastrointest Oncol. 2017;9(2):62–9.CrossRef
24.
go back to reference Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS, Tsai SJ. Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res. 2017;77(9):2339–50.CrossRef Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS, Tsai SJ. Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res. 2017;77(9):2339–50.CrossRef
25.
go back to reference Wang K, Sun Y, Tao W, Fei X, Chang C. Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals. Cancer Lett. 2017;394:1–12.CrossRef Wang K, Sun Y, Tao W, Fei X, Chang C. Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals. Cancer Lett. 2017;394:1–12.CrossRef
26.
go back to reference Yao Z, Luo J, Hu K, Lin J, Huang H, Wang Q, Zhang P, Xiong Z, He C, Huang Z, et al. ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways. Mol Oncol. 2017;11(4):422–37.CrossRef Yao Z, Luo J, Hu K, Lin J, Huang H, Wang Q, Zhang P, Xiong Z, He C, Huang Z, et al. ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways. Mol Oncol. 2017;11(4):422–37.CrossRef
27.
go back to reference Yang P, Qiu Z, Jiang Y, Dong L, Yang W, Gu C, Li G, Zhu Y. Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the Wnt/beta-catenin signaling pathway. Oncotarget. 2016;7(39):63449–55.PubMedPubMedCentral Yang P, Qiu Z, Jiang Y, Dong L, Yang W, Gu C, Li G, Zhu Y. Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the Wnt/beta-catenin signaling pathway. Oncotarget. 2016;7(39):63449–55.PubMedPubMedCentral
Metadata
Title
Up-regulation of circ_LARP4 suppresses cell proliferation and migration in ovarian cancer by regulating miR-513b-5p/LARP4 axis
Authors
Wumei Lin
Haiyan Ye
Keli You
Le Chen
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-1071-z

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine