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Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Cervical Cancer | Research

Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis

Authors: Zhihui Gao, Qianqing Wang, Mei Ji, Xiangcui Guo, Li Li, Xiaoke Su

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression.

Methods

CC stem cells (CD133+CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133+CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results.

Results

Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133+CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133+CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice.

Conclusion

Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells.
Appendix
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Literature
1.
go back to reference Small W Jr, et al. Cervical cancer: a global health crisis. Cancer. 2017;123(13):2404–12.CrossRef Small W Jr, et al. Cervical cancer: a global health crisis. Cancer. 2017;123(13):2404–12.CrossRef
2.
go back to reference Park S, et al. MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer. BMC Cancer. 2017;17(1):658.CrossRef Park S, et al. MiR-9, miR-21, and miR-155 as potential biomarkers for HPV positive and negative cervical cancer. BMC Cancer. 2017;17(1):658.CrossRef
3.
go back to reference Phuthong S, et al. Genetic polymorphism of the glutathione S-transferase Pi 1 (GSTP1) and susceptibility to cervical cancer in human papilloma virus infected northeastern Thai women. Asian Pac J Cancer Prev. 2018;19(2):381–5.PubMedPubMedCentral Phuthong S, et al. Genetic polymorphism of the glutathione S-transferase Pi 1 (GSTP1) and susceptibility to cervical cancer in human papilloma virus infected northeastern Thai women. Asian Pac J Cancer Prev. 2018;19(2):381–5.PubMedPubMedCentral
4.
go back to reference Nuchpramool P, Hanprasertpong J. preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are not clinically useful in predicting prognosis in early stage cervical cancer. Surg Res Pract. 2018;2018:9162921.PubMedPubMedCentral Nuchpramool P, Hanprasertpong J. preoperative neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are not clinically useful in predicting prognosis in early stage cervical cancer. Surg Res Pract. 2018;2018:9162921.PubMedPubMedCentral
5.
go back to reference Eleje GU, et al. Palliative interventions for controlling vaginal bleeding in advanced cervical cancer. Cochrane Database Syst Rev. 2019;3:CD011000.PubMed Eleje GU, et al. Palliative interventions for controlling vaginal bleeding in advanced cervical cancer. Cochrane Database Syst Rev. 2019;3:CD011000.PubMed
6.
go back to reference Chen S, et al. LncRNAs and their role in cancer stem cells. Oncotarget. 2017;8(66):110685–92.CrossRef Chen S, et al. LncRNAs and their role in cancer stem cells. Oncotarget. 2017;8(66):110685–92.CrossRef
7.
go back to reference Thery C. Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011;3:15.CrossRef Thery C. Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011;3:15.CrossRef
8.
go back to reference Wu XG, et al. Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma. Angiogenesis. 2019;22(3):397–410.CrossRef Wu XG, et al. Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma. Angiogenesis. 2019;22(3):397–410.CrossRef
9.
go back to reference Shang C, et al. Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer. Cancer Chemother Pharmacol. 2016;77(5):1061–7.CrossRef Shang C, et al. Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer. Cancer Chemother Pharmacol. 2016;77(5):1061–7.CrossRef
10.
go back to reference Fan L, et al. Long noncoding RNA urothelial cancer associated 1 regulates radioresistance via the hexokinase 2/glycolytic pathway in cervical cancer. Int J Mol Med. 2018;42(4):2247–59.PubMed Fan L, et al. Long noncoding RNA urothelial cancer associated 1 regulates radioresistance via the hexokinase 2/glycolytic pathway in cervical cancer. Int J Mol Med. 2018;42(4):2247–59.PubMed
11.
go back to reference Zhou Y, et al. IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p. Breast Cancer Res. 2018;20(1):32.CrossRef Zhou Y, et al. IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p. Breast Cancer Res. 2018;20(1):32.CrossRef
12.
go back to reference Zhang W, et al. Resveratrol chemosensitizes adriamycin-resistant breast cancer cells by modulating miR-122–5p. J Cell Biochem. 2019;120:16283.CrossRef Zhang W, et al. Resveratrol chemosensitizes adriamycin-resistant breast cancer cells by modulating miR-122–5p. J Cell Biochem. 2019;120:16283.CrossRef
13.
go back to reference Ding FN, et al. miR-122-5p modulates the radiosensitivity of cervical cancer cells by regulating cell division cycle 25A (CDC25A). FEBS Open Bio. 2019;9(11):1869–79.CrossRef Ding FN, et al. miR-122-5p modulates the radiosensitivity of cervical cancer cells by regulating cell division cycle 25A (CDC25A). FEBS Open Bio. 2019;9(11):1869–79.CrossRef
14.
go back to reference Li Y, Wang H, Huang H. Long non-coding RNA MIR205HG function as a ceRNA to accelerate tumor growth and progression via sponging miR-122-5p in cervical cancer. Biochem Biophys Res Commun. 2019;514(1):78–85.CrossRef Li Y, Wang H, Huang H. Long non-coding RNA MIR205HG function as a ceRNA to accelerate tumor growth and progression via sponging miR-122-5p in cervical cancer. Biochem Biophys Res Commun. 2019;514(1):78–85.CrossRef
15.
go back to reference Leis O, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 2012;31(11):1354–65.CrossRef Leis O, et al. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 2012;31(11):1354–65.CrossRef
16.
go back to reference Huang C, et al. SOX2 regulates radioresistance in cervical cancer via the hedgehog signaling pathway. Gynecol Oncol. 2018;151(3):533–41.CrossRef Huang C, et al. SOX2 regulates radioresistance in cervical cancer via the hedgehog signaling pathway. Gynecol Oncol. 2018;151(3):533–41.CrossRef
17.
go back to reference Chatterjee K, et al. Dietary polyphenols, resveratrol and pterostilbene exhibit antitumor activity on an HPV E6-positive cervical cancer model: an in vitro and in vivo analysis. Front Oncol. 2019;9:352.CrossRef Chatterjee K, et al. Dietary polyphenols, resveratrol and pterostilbene exhibit antitumor activity on an HPV E6-positive cervical cancer model: an in vitro and in vivo analysis. Front Oncol. 2019;9:352.CrossRef
19.
go back to reference Kim BW, et al. Clinical significance of OCT4 and SOX2 protein expression in cervical cancer. BMC Cancer. 2015;15:1015.CrossRef Kim BW, et al. Clinical significance of OCT4 and SOX2 protein expression in cervical cancer. BMC Cancer. 2015;15:1015.CrossRef
20.
go back to reference Cai C, et al. Expression of SOX2 in cervical intraepithelial neoplasia and cervical cancer and its clinical significance. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33(1):128–30.PubMed Cai C, et al. Expression of SOX2 in cervical intraepithelial neoplasia and cervical cancer and its clinical significance. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33(1):128–30.PubMed
21.
go back to reference Ren G, et al. Dendritic cells loaded with HeLa-derived exosomes simulate an antitumor immune response. Oncol Lett. 2018;15(5):6636–40.PubMedPubMedCentral Ren G, et al. Dendritic cells loaded with HeLa-derived exosomes simulate an antitumor immune response. Oncol Lett. 2018;15(5):6636–40.PubMedPubMedCentral
22.
go back to reference Wang X, et al. Fetal dermal mesenchymal stem cell-derived exosomes accelerate cutaneous wound healing by activating notch signaling. Stem Cells Int. 2019;2019:2402916.PubMedPubMedCentral Wang X, et al. Fetal dermal mesenchymal stem cell-derived exosomes accelerate cutaneous wound healing by activating notch signaling. Stem Cells Int. 2019;2019:2402916.PubMedPubMedCentral
23.
go back to reference He B, et al. Bioinformatics analysis of gene expression alterations in microRNA122 knockout mice with hepatocellular carcinoma. Mol Med Rep. 2017;15(6):3681–9.CrossRef He B, et al. Bioinformatics analysis of gene expression alterations in microRNA122 knockout mice with hepatocellular carcinoma. Mol Med Rep. 2017;15(6):3681–9.CrossRef
24.
go back to reference Luan Y, et al. Circulating lncRNA UCA1 promotes malignancy of colorectal cancer via the miR-143/MYO6 Axis. Mol Ther Nucleic Acids. 2020;19:790–803.CrossRef Luan Y, et al. Circulating lncRNA UCA1 promotes malignancy of colorectal cancer via the miR-143/MYO6 Axis. Mol Ther Nucleic Acids. 2020;19:790–803.CrossRef
25.
go back to reference Yu Y, et al. lncRNA UCA1 functions as a ceRNA to promote prostate cancer progression via sponging miR143. Mol Ther Nucleic Acids. 2020;19:751–8.CrossRef Yu Y, et al. lncRNA UCA1 functions as a ceRNA to promote prostate cancer progression via sponging miR143. Mol Ther Nucleic Acids. 2020;19:751–8.CrossRef
26.
go back to reference Wang CJ, et al. The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer. 2019;18(1):115.CrossRef Wang CJ, et al. The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer. 2019;18(1):115.CrossRef
27.
go back to reference Pei ZJ, et al. miR-122-5p inhibits tumor cell proliferation and induces apoptosis by targeting MYC in gastric cancer cells. Pharmazie. 2017;72(6):344–7.PubMed Pei ZJ, et al. miR-122-5p inhibits tumor cell proliferation and induces apoptosis by targeting MYC in gastric cancer cells. Pharmazie. 2017;72(6):344–7.PubMed
28.
go back to reference Xu Z, et al. miR-122-5p inhibits the proliferation, invasion and growth of bile duct carcinoma cells by targeting ALDOA. Cell Physiol Biochem. 2018;48(6):2596–606.CrossRef Xu Z, et al. miR-122-5p inhibits the proliferation, invasion and growth of bile duct carcinoma cells by targeting ALDOA. Cell Physiol Biochem. 2018;48(6):2596–606.CrossRef
29.
go back to reference Su R, et al. Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122. Mol Cancer. 2017;16(1):171.CrossRef Su R, et al. Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122. Mol Cancer. 2017;16(1):171.CrossRef
30.
go back to reference Xu X, et al. MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4. Cancer Biol Ther. 2018;19(5):427–35.CrossRef Xu X, et al. MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4. Cancer Biol Ther. 2018;19(5):427–35.CrossRef
Metadata
Title
Exosomal lncRNA UCA1 modulates cervical cancer stem cell self-renewal and differentiation through microRNA-122-5p/SOX2 axis
Authors
Zhihui Gao
Qianqing Wang
Mei Ji
Xiangcui Guo
Li Li
Xiaoke Su
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-02872-9

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