Home LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
Article
Licensed
Unlicensed Requires Authentication

LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma

  • Qing Li , Wei Wang , Tao Yang , Dongsheng Li , Yinpeng Huang , Guang Bai and Qiang Li EMAIL logo
Published/Copyright: January 31, 2022
Biological Chemistry
From the journal Biological Chemistry Volume 403 Issue 7

Abstract

Hepatocellular carcinoma (HCC) is one of the most common human cancers. Long non-coding RNA (lncRNA) has been demonstrated to play an important role in regulating tumor development. The current study aims to explore the specific role of LINC00520 during HCC progression. The present study identified that LINC00520 was upregulated in HCC tissues and indicated poor patient survival. Overexpression of LINC00520 promoted HCC cell proliferation, migration and invasion, while LINC00520 downregulation led to the opposite effects. Besides, LINC00520 knockdown was found to inhibit tumor growth in vivo. Furthermore, LINC00520 acted as a sponge of miR-4516 to regulate SRY-related high mobility group box 5 (SOX5). In addition, the inhibition of miR-4516 partly reversed the inhibitory effect of LINC00520 silencing on HCC cell proliferation, migration and invasion. In conclusion, the inhibition of LINC00520 suppressed HCC cell proliferation, migration and invasion through mediating miR-4516/SOX5 axis. Therefore, our study provides a basis for the development of treatment strategies for HCC.

Keywords: hepatocellular carcinoma; invasion; LINC00520; miR-4516; proliferation; SOX5
Corresponding author: Qiang Li, Department of General Surgery, First Affiliated Hospital of Jinzhou Medical University, No. 2, section 5, Renmin Street Guta District, Jinzhou 121000, China, E-mail:
Wei Wang and Qing Li contributed equally to this work.

Funding source: Liaoning Provincial Education Office FundLiaoning Provincial Science and Technology Department FundLiaoning Provincial Science and Technology Department Fund

Award Identifier / Grant number: JYTQN2020038

Award Identifier / Grant number: 2019-ZD-0830

Award Identifier / Grant number: 2020-MS-294

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported by Liaoning Provincial Education Office Fund (JYTQN2020038, Liaoning Provincial Science and Technology Department Fund (2020-MS-294) and Liaoning Provincial Science and Technology Department Fund (2019-ZD-0830).

  3. Conflict of interest statement: None.

References

Chen, R., Chen, Y., Huang, W., Zhao, Y., Luo, W., Lin, J., Wang, Z., and Yang, J. (2021). Comprehensive analysis of an immune-related ceRNA network in identifying a novel lncRNA signature as a prognostic biomarker for hepatocellular carcinoma. Aging 13: 17607–17628, https://doi.org/10.18632/aging.203250.Search in Google Scholar PubMed PubMed Central

Chen, S., Xu, M., Zhao, J., Shen, J., Li, J., Liu, Y., Cao, G., Ma, J., He, W., Chen, X., et al.. (2020). MicroRNA-4516 suppresses pancreatic cancer development via negatively regulating orthodenticle homeobox 1. Int. J. Biol. Sci. 16: 2159–2169, https://doi.org/10.7150/ijbs.45933.Search in Google Scholar PubMed PubMed Central

Chen, X., Fu, Y., Xu, H., Teng, P., Xie, Q., Zhang, Y., Yan, C., Xu, Y., Li, C., Zhou, J., et al.. (2018). SOX5 predicts poor prognosis in lung adenocarcinoma and promotes tumor metastasis through epithelial-mesenchymal transition. Oncotarget 9: 10891–10904, https://doi.org/10.18632/oncotarget.22443.Search in Google Scholar PubMed PubMed Central

Chu, J., Geng, G., Ai, X., Jia, W., Wang, J., Xu, B., Kong, X., and Kong, L. (2021). LINC01291 promotes hepatocellular carcinoma development by targeting miR-186-5p/OXSR1 axis. J. Gene Med.: e3394, https://doi.org/10.1002/jgm.3394.Search in Google Scholar PubMed

Cui, T., Bell, E.H., Mcelroy, J., Becker, A.P., Gulati, P.M., Geurts, M., Mladkova, N., Gray, A., Liu, K., Yang, L., et al.. (2019). miR-4516 predicts poor prognosis and functions as a novel oncogene via targeting PTPN14 in human glioblastoma. Oncogene 38: 2923–2936, https://doi.org/10.1038/s41388-018-0601-9.Search in Google Scholar PubMed PubMed Central

Du, M., Wang, W., Jin, H., Wang, Q., Ge, Y., Lu, J., Ma, G., Chu, H., Tong, N., Zhu, H., et al.. (2015). The association analysis of lncRNA HOTAIR genetic variants and gastric cancer risk in a Chinese population. Oncotarget 6: 31255–31262, https://doi.org/10.18632/oncotarget.5158.Search in Google Scholar PubMed PubMed Central

Galle, P.R. (2008). Sorafenib in advanced hepatocellular carcinoma – we have won a battle not the war. J. Hepatol. 49: 871–873, https://doi.org/10.1016/j.jhep.2008.09.001.Search in Google Scholar PubMed

Henry, W.S., Hendrickson, D.G., Beca, F., Glass, B., Lindahl-Allen, M., He, L., Ji, Z., Struhl, K., Beck, A.H., Rinn, J.L., et al.. (2016). LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer. Oncotarget 7: 81981–81994, https://doi.org/10.18632/oncotarget.11962.Search in Google Scholar PubMed PubMed Central

Hu, J., Tian, J., Zhu, S., Sun, L., Yu, J., Tian, H., Dong, Q., Luo, Q., Jiang, N., Niu, Y., et al.. (2018). Sox5 contributes to prostate cancer metastasis and is a master regulator of TGF-beta-induced epithelial mesenchymal transition through controlling Twist1 expression. Br. J. Cancer 118: 88–97, https://doi.org/10.1038/bjc.2017.372.Search in Google Scholar PubMed PubMed Central

Huang, W., Wang, X., Wu, F., and Xu, F. (2021). LncRNA LINC00520 aggravates cell proliferation and migration in lung adenocarcinoma via a positive feedback loop. BMC Pulm. Med. 21: 287, https://doi.org/10.1186/s12890-021-01657-6.Search in Google Scholar PubMed PubMed Central

Jin, X.H., Hong, Y.G., Li, P., Hao, L.Q., and Chen, M. (2020). Long noncoding RNA LINC00520 accelerates the progression of colorectal cancer by serving as a competing endogenous RNA of microRNA-577 to increase HSP27 expression. Hum. Cell 33: 683–694, https://doi.org/10.1007/s13577-020-00336-8.Search in Google Scholar PubMed

Li, O., Li, Z., Tang, Q., Li, Y., Yuan, S., Shen, Y., Zhang, Z., Li, N., Chu, K., and Lei, G. (2018). Long stress induced non-coding transcripts 5 (LSINCT5) promotes hepatocellular carcinoma progression through interaction with high-mobility group AT-hook 2 and MiR-4516. Med. Sci. Mon. Int. Med. J. Exp. Clin. Res. 24: 8510–8523, https://doi.org/10.12659/msm.911179.Search in Google Scholar

Lu, X., Guo, H., Molter, J., Miao, H., Gerber, L., Hu, Y., Barnes, E.L., Vogel, H., Lee, Z., Luo, G., et al.. (2011). Alpha-fetoprotein-thymidine kinase-luciferase knockin mice: a novel model for dual modality longitudinal imaging of tumorigenesis in liver. J. Hepatol. 55: 96–102, https://doi.org/10.1016/j.jhep.2010.10.020.Search in Google Scholar PubMed PubMed Central

Luan, W., Ding, Y., Yuan, H., Ma, S., Ruan, H., Wang, J., Lu, F., and Bu, X. (2020). Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis. J. Exp. Clin. Cancer Res. 39: 96, https://doi.org/10.1186/s13046-020-01599-7.Search in Google Scholar PubMed PubMed Central

Ma, Y., Bian, J., and Zhang, F. (2016). Inhibition of perillyl alcohol on cell invasion and migration depends on the Notch signaling pathway in hepatoma cells. Mol. Cell. Biochem. 411: 307–315, https://doi.org/10.1007/s11010-015-2593-x.Search in Google Scholar PubMed

Pan, W., Liu, L., Wei, J., Ge, Y., Zhang, J., Chen, H., Zhou, L., Yuan, Q., Zhou, C., and Yang, M. (2016). A functional lncRNA HOTAIR genetic variant contributes to gastric cancer susceptibility. Mol. Carcinog. 55: 90–96, https://doi.org/10.1002/mc.22261.Search in Google Scholar PubMed

Pei, X.H., Lv, X.Q., and Li, H.X. (2014). Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1. Biochem. Biophys. Res. Commun. 446: 322–327, https://doi.org/10.1016/j.bbrc.2014.02.109.Search in Google Scholar PubMed

Ren, Z., Ma, X., Duan, Z., and Chen, X. (2020). Diagnosis, therapy, and prognosis for hepatocellular carcinoma. Anal. Cell Pathol. 2020:pp. 8157406, https://doi.org/10.1155/2020/8157406.Search in Google Scholar PubMed PubMed Central

Renjie, W. and Haiqian, L. (2015). MiR-132, miR-15a and miR-16 synergistically inhibit pituitary tumor cell proliferation, invasion and migration by targeting Sox5. Cancer Lett. 356: 568–578, https://doi.org/10.1016/j.canlet.2014.10.003.Search in Google Scholar PubMed

Shommo, G. and Apolloni, B. (2021). A holistic miRNA-mRNA module discovery. Non-coding RNA Res. 6: 159–166, https://doi.org/10.1016/j.ncrna.2021.09.001.Search in Google Scholar PubMed PubMed Central

Sun, Y., Shi, T., Ma, Y., Qin, H., and Li, K. (2020). Long noncoding RNA LINC00520 accelerates progression of papillary thyroid carcinoma by serving as a competing endogenous RNA of microRNA-577 to increase Sphk2 expression. Cell Cycle 19: 787–800, https://doi.org/10.1080/15384101.2020.1731062.Search in Google Scholar PubMed PubMed Central

Tan, F.L., Tan, Y.M., Chung, A.Y., Cheow, P.C., Chow, P.K., and Ooi, L.L. (2006). Factors affecting early mortality in spontaneous rupture of hepatocellular carcinoma. ANZ J. Surg. 76: 448–452, https://doi.org/10.1111/j.1445-2197.2006.03750.x.Search in Google Scholar PubMed

Wang, D., Han, S., Wang, X., Peng, R., and Li, X. (2015). SOX5 promotes epithelial-mesenchymal transition and cell invasion via regulation of Twist1 in hepatocellular carcinoma. Med. Oncol. 32: 461, https://doi.org/10.1007/s12032-014-0461-2.Search in Google Scholar PubMed

Wang, J.F., Xi, Z.N., Su, H.J., Bao, Z., and Qiao, Y.H. (2021). SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis. Hum. Cell 34: 952–964, https://doi.org/10.1007/s13577-021-00518-y.Search in Google Scholar PubMed

Wang, Y., Yang, C., Liu, X., Zheng, J., Zhang, F., Wang, D., Xue, Y., Li, X., Shen, S., Shao, L., et al.. (2020). Transcription factor AP-4 (TFAP4)-upstream ORF coding 66 aa inhibits the malignant behaviors of glioma cells by suppressing the TFAP4/long noncoding RNA 00520/microRNA-520f-3p feedback loop. Cancer Sci. 111: 891–906, https://doi.org/10.1111/cas.14308.Search in Google Scholar PubMed PubMed Central

Wang, Z. and Xu, R. (2020). lncRNA PART1 promotes breast cancer cell progression by directly targeting miR-4516. Cancer Manag. Res. 12: 7753–7760, https://doi.org/10.2147/cmar.s249296.Search in Google Scholar

Wei, H., Tang, Q., Wang, A., Zhang, Y., Qin, Z., Li, W., Xu, Z., Wang, J., and Pu, J. (2021). lncRNA MAGI2-AS3 exerts antioncogenic roles in hepatocellular carcinoma via regulating the miR-519c-3p/TXNIP Axis. JAMA Oncol. 2021: 5547345, https://doi.org/10.1155/2021/5547345.Search in Google Scholar PubMed PubMed Central

Xia, G., Li, X., Chen, F., and Shao, Z. (2020). LncRNA LINC00520 predicts poor prognosis and promotes progression of lung cancer by inhibiting MiR-3175 expression. Cancer Manag. Res. 12: 5741–5748, https://doi.org/10.2147/cmar.s250631.Search in Google Scholar PubMed PubMed Central

Xiang, J.F., Yin, Q.F., Chen, T., Zhang, Y., Zhang, X.O., Wu, Z., Zhang, S., Wang, H.B., Ge, J., Lu, X., et al.. (2014). Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 24: 513–531, https://doi.org/10.1038/cr.2014.35.Search in Google Scholar PubMed PubMed Central

Xie, T., Pi, G., Yang, B., Ren, H., Yu, J., Ren, Q., Zhou, X., Hu, D., Zhang, H., Zhang, H., et al.. (2019). Long non-coding RNA 520 is a negative prognostic biomarker and exhibits pro-oncogenic function in nasopharyngeal carcinoma carcinogenesis through regulation of miR-26b-3p/USP39 axis. Gene 707: 44–52, https://doi.org/10.1016/j.gene.2019.02.093.Search in Google Scholar PubMed

Zhang, D. and Liu, S. (2017). SOX5 promotes epithelial-mesenchymal transition in osteosarcoma via regulation of Snail. J BUON 22: 258–264.Search in Google Scholar

Zhao, H., Bi, M., Lou, M., Yang, X., and Sun, L. (2021). Downregulation of SOX2-OT prevents hepatocellular carcinoma progression through miR-143-3p/MSI2. Front. Oncol. 11: 685912, https://doi.org/10.3389/fonc.2021.685912.Search in Google Scholar PubMed PubMed Central

Zhou, X., Ye, F., Yin, C., Zhuang, Y., Yue, G., and Zhang, G. (2015). The interaction between MiR-141 and lncRNA-H19 in regulating cell proliferation and migration in gastric cancer. Cell. Physiol. Biochem. 36: 1440–1452, https://doi.org/10.1159/000430309.Search in Google Scholar PubMed

Zhou, Y., Li, K., Zou, X., Hua, Z., Wang, H., Bian, W., Wang, H., Chen, F. and Dai, T. (2021). LncRNA DHRS4-AS1 ameliorates hepatocellular carcinoma by suppressing proliferation and promoting apoptosis via miR-522-3p/SOCS5 axis. Bioengineered 12: 10862–10877, https://doi.org/10.1080/21655979.2021.1994719.Search in Google Scholar PubMed PubMed Central

Received: 2021-07-11
Revised: 2021-12-18
Accepted: 2022-01-05
Published Online: 2022-01-31
Published in Print: 2022-06-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Chemerin – exploring a versatile adipokine
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study
  7. Cell Biology and Signaling
  8. SRPK1 promotes cell proliferation and tumor growth of osteosarcoma through activation of the NF-κB signaling pathway
  9. LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
  10. Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
  11. CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
https://doi.org/10.1515/hsz-2021-0316
Keywords for this article
hepatocellular carcinoma; invasion; LINC00520; miR-4516; proliferation; SOX5

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Chemerin – exploring a versatile adipokine
  4. Research Articles/Short Communications
  5. Protein Structure and Function
  6. Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study
  7. Cell Biology and Signaling
  8. SRPK1 promotes cell proliferation and tumor growth of osteosarcoma through activation of the NF-κB signaling pathway
  9. LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
  10. Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
  11. CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 27.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/hsz-2021-0316/html?lang=en
Scroll to top button