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Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Colorectal Cancer | Research article

Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

Authors: Caihong Wen, Xiaoqing Feng, Honggang Yuan, Yong Gong, Guangsheng Wang

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation.

Methods

Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot.

Results

Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p.

Conclusion

Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.
Appendix
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Literature
1.
go back to reference Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet (London, England). 2019;394(10207):1467–80.CrossRef Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet (London, England). 2019;394(10207):1467–80.CrossRef
2.
go back to reference Geng Y, Zheng X, Hu W, Wang Q, Xu Y, He W, et al. Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression. Clin Sci (London, England : 1979). 2019;133(10):1197–213.CrossRef Geng Y, Zheng X, Hu W, Wang Q, Xu Y, He W, et al. Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression. Clin Sci (London, England : 1979). 2019;133(10):1197–213.CrossRef
3.
go back to reference Weinberg BA, Marshall JL, Salem ME. The Growing Challenge of Young Adults With Colorectal Cancer. Oncology (Williston Park, NY). 2017;31(5):381–9. Weinberg BA, Marshall JL, Salem ME. The Growing Challenge of Young Adults With Colorectal Cancer. Oncology (Williston Park, NY). 2017;31(5):381–9.
4.
go back to reference Yiu AJ, Yiu CY. Biomarkers in colorectal Cancer. Anticancer Res. 2016;36(3):1093–102.PubMed Yiu AJ, Yiu CY. Biomarkers in colorectal Cancer. Anticancer Res. 2016;36(3):1093–102.PubMed
5.
go back to reference Lech G, Słotwiński R, Słodkowski M, Krasnodębski IW. Colorectal cancer tumour markers and biomarkers: recent therapeutic advances. World J Gastroenterol. 2016;22(5):1745–55.CrossRef Lech G, Słotwiński R, Słodkowski M, Krasnodębski IW. Colorectal cancer tumour markers and biomarkers: recent therapeutic advances. World J Gastroenterol. 2016;22(5):1745–55.CrossRef
6.
go back to reference You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015;18(4):603–10. You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015;18(4):603–10.
7.
go back to reference Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N, Giusti S, et al. Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. Mol Cell. 2015;58(5):870–85. Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N, Giusti S, et al. Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed. Mol Cell. 2015;58(5):870–85.
8.
go back to reference Bach DH, Lee SK, Sood AK. Circular RNAs in Cancer. Mol Ther Nucleic Acids. 2019;16:118–29.CrossRef Bach DH, Lee SK, Sood AK. Circular RNAs in Cancer. Mol Ther Nucleic Acids. 2019;16:118–29.CrossRef
9.
go back to reference Zhu X, Wang X, Wei S, Chen Y, Chen Y, Fan X, et al. hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma. FEBS J. 2017;284(14):2170–82.CrossRef Zhu X, Wang X, Wei S, Chen Y, Chen Y, Fan X, et al. hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma. FEBS J. 2017;284(14):2170–82.CrossRef
10.
go back to reference Ge J, Jin Y, Lv X, Liao Q, Luo C, Ye G, et al. Expression profiles of circular RNAs in human colorectal cancer based on RNA deep sequencing. J Clin Lab Anal. 2019;33(7):e22952.CrossRef Ge J, Jin Y, Lv X, Liao Q, Luo C, Ye G, et al. Expression profiles of circular RNAs in human colorectal cancer based on RNA deep sequencing. J Clin Lab Anal. 2019;33(7):e22952.CrossRef
11.
go back to reference Panda AC. Circular RNAs act as miRNA sponges. Adv Exp Med Biol. 2018;1087:67–79.CrossRef Panda AC. Circular RNAs act as miRNA sponges. Adv Exp Med Biol. 2018;1087:67–79.CrossRef
12.
go back to reference Wu HB, Huang SS, Lu CG, Tian SD, Chen M. CircAPLP2 regulates the proliferation and metastasis of colorectal cancer by targeting miR-101-3p to activate the notch signalling pathway. Am J Transl Res. 2020;12(6):2554–69.PubMedPubMedCentral Wu HB, Huang SS, Lu CG, Tian SD, Chen M. CircAPLP2 regulates the proliferation and metastasis of colorectal cancer by targeting miR-101-3p to activate the notch signalling pathway. Am J Transl Res. 2020;12(6):2554–69.PubMedPubMedCentral
13.
go back to reference Zhang L, Dong X, Yan B, Yu W, Shan L. CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1. Cell Death Dis. 2020;11(7):542.CrossRef Zhang L, Dong X, Yan B, Yu W, Shan L. CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1. Cell Death Dis. 2020;11(7):542.CrossRef
14.
go back to reference Li L, Zhang X, Yi Z, Liang X, Yin W, Li S. MiR-503 promotes the migration and invasion of colorectal cancer cells by regulating PDCD4. J BUON. 2018;23(3):579–86.PubMed Li L, Zhang X, Yi Z, Liang X, Yin W, Li S. MiR-503 promotes the migration and invasion of colorectal cancer cells by regulating PDCD4. J BUON. 2018;23(3):579–86.PubMed
15.
go back to reference Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16(1):94.CrossRef Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16(1):94.CrossRef
16.
go back to reference Yin Y, Long J, He Q, Li Y, Liao Y, He P, et al. Emerging roles of circRNA in formation and progression of cancer. J Cancer. 2019;10(21):5015–21.CrossRef Yin Y, Long J, He Q, Li Y, Liao Y, He P, et al. Emerging roles of circRNA in formation and progression of cancer. J Cancer. 2019;10(21):5015–21.CrossRef
17.
go back to reference Du WW, Fang L, Yang W, Wu N, Awan FM, Yang Z, et al. Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ. 2017;24(2):357–70.CrossRef Du WW, Fang L, Yang W, Wu N, Awan FM, Yang Z, et al. Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ. 2017;24(2):357–70.CrossRef
18.
go back to reference Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56(1):55–66.CrossRef Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56(1):55–66.CrossRef
19.
go back to reference Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20(11):675–91.CrossRef Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20(11):675–91.CrossRef
20.
go back to reference Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, et al. CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 2018;9(4):417.CrossRef Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, et al. CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 2018;9(4):417.CrossRef
21.
go back to reference Yang G, Zhang T, Ye J, Yang J, Chen C, Cai S, et al. Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation. Cancer Manag Res. 2019;11:6499–509.CrossRef Yang G, Zhang T, Ye J, Yang J, Chen C, Cai S, et al. Circ-ITGA7 sponges miR-3187-3p to upregulate ASXL1, suppressing colorectal cancer proliferation. Cancer Manag Res. 2019;11:6499–509.CrossRef
22.
go back to reference Deb B, Uddin A, Chakraborty S. miRNAs and ovarian cancer: an overview. J Cell Physiol. 2018;233(5):3846–54.CrossRef Deb B, Uddin A, Chakraborty S. miRNAs and ovarian cancer: an overview. J Cell Physiol. 2018;233(5):3846–54.CrossRef
23.
go back to reference Huang L, Zhang Y, Li Z, Zhao X, Xi Z, Chen H, et al. MiR-4319 suppresses colorectal cancer progression by targeting ABTB1. United European Gastroenterol J. 2019;7(4):517–28.CrossRef Huang L, Zhang Y, Li Z, Zhao X, Xi Z, Chen H, et al. MiR-4319 suppresses colorectal cancer progression by targeting ABTB1. United European Gastroenterol J. 2019;7(4):517–28.CrossRef
24.
go back to reference Jin C, Wang A, Liu L, Wang G, Li G. Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis. J Cell Physiol. 2019;234(5):7247–56.CrossRef Jin C, Wang A, Liu L, Wang G, Li G. Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis. J Cell Physiol. 2019;234(5):7247–56.CrossRef
25.
go back to reference Jiang SP, Li ZR. MiR-503-5p regulates cell epithelial-to-mesenchymal transition, metastasis and prognosis of hepatocellular carcinoma through inhibiting WEE1. Eur Rev Med Pharmacol Sci. 2019;23(5):2028–37.PubMed Jiang SP, Li ZR. MiR-503-5p regulates cell epithelial-to-mesenchymal transition, metastasis and prognosis of hepatocellular carcinoma through inhibiting WEE1. Eur Rev Med Pharmacol Sci. 2019;23(5):2028–37.PubMed
26.
go back to reference Li X, Han X, Yang J, Sun J, Wei P. miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33(10):1360–4.PubMed Li X, Han X, Yang J, Sun J, Wei P. miR-503-5p inhibits the proliferation of T24 and EJ bladder cancer cells by interfering with the Rb/E2F signaling pathway. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33(10):1360–4.PubMed
27.
go back to reference Ran W, Zeng YH, Ma XJ, Liao P, Liu XL. The Effect of miR-503-5p on the Proliferation, Invasion, Migration and Epithelial Interstitium of Cervical Cancer HeLa Cells via Targeting E2 F3. Sichuan Da Xue Xue Bao Yi Xue Ban. 2020;51(2):178–84.PubMed Ran W, Zeng YH, Ma XJ, Liao P, Liu XL. The Effect of miR-503-5p on the Proliferation, Invasion, Migration and Epithelial Interstitium of Cervical Cancer HeLa Cells via Targeting E2 F3. Sichuan Da Xue Xue Bao Yi Xue Ban. 2020;51(2):178–84.PubMed
28.
go back to reference Han L, Cheng J, Li A. hsa_circ_0072387 suppresses proliferation, metastasis, and glycolysis of Oral squamous cell carcinoma cells by Downregulating miR-503-5p. Cancer Biother Radiopharm. 2020. Han L, Cheng J, Li A. hsa_circ_0072387 suppresses proliferation, metastasis, and glycolysis of Oral squamous cell carcinoma cells by Downregulating miR-503-5p. Cancer Biother Radiopharm. 2020.
29.
go back to reference Zeng T, Zhang Q, Yu X, Gao X, Qiu Y. Inhibition of cell migration and invasion and promotion of cell apoptosis by overexpression of programmed cell death 4 (PDCD4) in cervical cancer Siha cells. Int J Clin Exp Pathol. 2018;11(9):4676–83.PubMedPubMedCentral Zeng T, Zhang Q, Yu X, Gao X, Qiu Y. Inhibition of cell migration and invasion and promotion of cell apoptosis by overexpression of programmed cell death 4 (PDCD4) in cervical cancer Siha cells. Int J Clin Exp Pathol. 2018;11(9):4676–83.PubMedPubMedCentral
30.
go back to reference Wang Q, Zhu J, Wang YW, Dai Y, Wang YL, Wang C, et al. Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon carcinoma. Oncogene. 2017;36(45):6225–34.CrossRef Wang Q, Zhu J, Wang YW, Dai Y, Wang YL, Wang C, et al. Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon carcinoma. Oncogene. 2017;36(45):6225–34.CrossRef
31.
go back to reference Montero H, Pérez-Gil G, Sampieri CL. Eukaryotic initiation factor 4A (eIF4A) during viral infections. Virus Genes. 2019;55(3):267–73.CrossRef Montero H, Pérez-Gil G, Sampieri CL. Eukaryotic initiation factor 4A (eIF4A) during viral infections. Virus Genes. 2019;55(3):267–73.CrossRef
33.
go back to reference Huang H, Wang X, Wang C, Zhuo L, Luo S, Han S. The miR-93 promotes proliferation by directly targeting PDCD4 in hepatocellular carcinoma. Neoplasma. 2017;64(5):770–7.CrossRef Huang H, Wang X, Wang C, Zhuo L, Luo S, Han S. The miR-93 promotes proliferation by directly targeting PDCD4 in hepatocellular carcinoma. Neoplasma. 2017;64(5):770–7.CrossRef
34.
go back to reference Wang Y, Liu Z, Shen J. MicroRNA-421-targeted PDCD4 regulates breast cancer cell proliferation. Int J Mol Med. 2019;43(1):267–75.CrossRef Wang Y, Liu Z, Shen J. MicroRNA-421-targeted PDCD4 regulates breast cancer cell proliferation. Int J Mol Med. 2019;43(1):267–75.CrossRef
35.
go back to reference Yin Y, Zhao B, Li D, Yin G. Long non-coding RNA CASC15 promotes melanoma progression by epigenetically regulating PDCD4. Cell Biosci. 2018;8:42.CrossRef Yin Y, Zhao B, Li D, Yin G. Long non-coding RNA CASC15 promotes melanoma progression by epigenetically regulating PDCD4. Cell Biosci. 2018;8:42.CrossRef
Metadata
Title
Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression
Authors
Caihong Wen
Xiaoqing Feng
Honggang Yuan
Yong Gong
Guangsheng Wang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07997-0

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