Skip to main content

Advertisement

Log in

Knockdown of SUMO1P3 represses tumor growth and invasion and enhances radiosensitivity in hepatocellular carcinoma

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with high recurrence and metastasis rates. Radiotherapy represents a major therapeutic option for HCC patients. However, the efficacy of radiotherapy has been limited due to the development of intrinsic radioresistance of the tumor cells. Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3), one member of SUMO pseudogene family, is a novel identified lncRNA that was originally identified to be upregulated in gastric cancer. However, the detailed roles of SUMO1P3 in HCC development remain to be elucidated. Here, the expression of SUMO1P3 in HCC tissues and cells was examined by qRT-PCR. Cell proliferation, colony formation ability, invasion ability, apoptosis, and radiosensitivity were detected by MTT assay, colony formation assay, cell invasion assay, flow cytometry analysis, and survival fraction assay, respectively. We found that SUMO1P3 was significantly upregulated in HCC tissues and cells. Besides, SUMO1P3 was highly expressed in HCC patients with higher TNM stage. Furthermore, SUMO1P3 knockdown markedly suppressed cell proliferation, colony formation ability, and cell invasiveness, promoted apoptosis, and enhanced radiosensitivity of HCC cells. We concluded that the knockdown of SUMO1P3 repressed tumor growth, invasion, promoted apoptosis, and enhanced radiosensitivity in HCC, providing evidence that SUMO1P3 might be a potential novel biomarker and a therapeutic target for HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

SUMO1P3:

Small ubiquitin-like modifier 1 pseudogene 3

LncRNAs:

Long non-coding RNAs

WHO:

World Health Organization

TNM:

Tumor-node-metastasis

DMEM:

Dulbecco’s Modified Eagle’s Medium

FBS:

Fetal bovine serum

qRT-PCR:

Quantitative real-time polymerase chain reaction

cDNA:

Complementary DNA

DMSO:

Dimethyl sulfoxide

ANOVA:

One-way analysis of variance

GAS5:

LncRNA growth arrest-specific 5

CCAT1:

LncRNA colon cancer-associated transcript-1

CRNDE:

LncRNA colorectal neoplasia differentially expressed

HMGB1:

High-mobility group box 1 protein

References

  1. Ferlay J et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917

    Article  CAS  PubMed  Google Scholar 

  2. El-Serag HB et al (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576

    Article  CAS  PubMed  Google Scholar 

  3. Rampone B et al (2009) Current management strategy of hepatocellular carcinoma. World J Gastroenterol 15(26):3210–3216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Seo YS et al (2010) Preliminary result of stereotactic body radiotherapy as a local salvage treatment for inoperable hepatocellular carcinoma. J Surg Oncol 102(3):209–214

    Article  PubMed  Google Scholar 

  5. Yu JI et al (2014) Considerations for radiation therapy in hepatocellular carcinoma: the radiation oncologists’ perspective. Dig Dis 32(6):755–763

    Article  PubMed  Google Scholar 

  6. Kalogeridi MA et al (2015) Role of radiotherapy in the management of hepatocellular carcinoma: a systematic review. World J Hepatol 7(1):101–112

    Article  PubMed  PubMed Central  Google Scholar 

  7. Toya R et al (2007) Conformal radiation therapy for portal vein tumor thrombosis of hepatocellular carcinoma. Radiother Oncol 84(3):266–271

    Article  PubMed  Google Scholar 

  8. Rodemann HP (2009) Molecular radiation biology: perspectives for radiation oncology. Radiother Oncol 92(3):293–298

    Article  PubMed  Google Scholar 

  9. Cun Y et al (2013) Silencing of APE1 enhances sensitivity of human hepatocellular carcinoma cells to radiotherapy in vitro and in a xenograft model. PLoS ONE 8(2):e55313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ursino S et al (2012) Radiotherapy and hepatocellular carcinoma: update and review of the literature. Eur Rev Med Pharmacol Sci 16(11):1599–1604

    CAS  PubMed  Google Scholar 

  11. Li JK et al (2017) Long noncoding RNA MRCCAT1 promotes metastasis of clear cell renal cell carcinoma via inhibiting NPR3 and activating p38-MAPK signaling. Mol Cancer 16(1):111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guttman M et al (2012) Modular regulatory principles of large non-coding RNAs. Nature 482(7385):339–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Quan M et al (2015) Exploring the secrets of long noncoding RNAs. Int J Mol Sci 16(3):5467–5496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Schmitt AM et al (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29(4):452–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mercer TR et al (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  PubMed  Google Scholar 

  16. Yan X et al (2015) Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell 28(4):529–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tan J et al (2015) Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells. FEBS Lett 589(20 Pt B):3175–3181

    Article  CAS  PubMed  Google Scholar 

  18. Lu Y et al (2016) The long non-coding RNA NEAT1 regulates epithelial to mesenchymal transition and radioresistance in through miR-204/ZEB1 axis in nasopharyngeal carcinoma. Tumour Biol 37(9):11733–11741

    Article  CAS  PubMed  Google Scholar 

  19. Bettermann K et al (2012) SUMOylation in carcinogenesis. Cancer Lett 316(2):113–125

    Article  CAS  PubMed  Google Scholar 

  20. Su HL et al (2002) Molecular features of human ubiquitin-like SUMO genes and their encoded proteins. Gene 296(1–2):65–73

    Article  CAS  PubMed  Google Scholar 

  21. Pink RC et al. (2011) Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 17(5): 792–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Li PF et al (2014) Non-coding RNAs and gastric cancer. World J Gastroenterol 20(18):5411–5419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mei D et al (2013) Up-regulation of SUMO1 pseudogene 3 (SUMO1P3) in gastric cancer and its clinical association. Med Oncol 30(4):709

    Article  CAS  PubMed  Google Scholar 

  24. Zhan Y et al (2016) Increased expression of SUMO1P3 predicts poor prognosis and promotes tumor growth and metastasis in bladder cancer. Oncotarget 7(13):16038–16048

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li D et al (2014) Minimally invasive local therapies for liver cancer. Cancer Biol Med 11(4):217–236

    PubMed  PubMed Central  Google Scholar 

  26. Liu YR et al (2015) Long noncoding RNAs in hepatocellular carcinoma: novel insights into their mechanism. World J Hepatol 7(28):2781–2791

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chang L et al (2016) Decreased expression of long non-coding RNA GAS5 indicates a poor prognosis and promotes cell proliferation and invasion in hepatocellular carcinoma by regulating vimentin. Mol Med Rep 13(2):1541–1550

    Article  CAS  PubMed  Google Scholar 

  28. Deng L et al (2015) Long noncoding RNA CCAT1 promotes hepatocellular carcinoma progression by functioning as let-7 sponge. J Exp Clin Cancer Res 34:18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chen Z et al (2016) LncRNA CRNDE promotes hepatic carcinoma cell proliferation, migration and invasion by suppressing miR-384. Am J Cancer Res 6(10):2299–2309

    PubMed  PubMed Central  Google Scholar 

  30. Hu X et al (2017) Downregulation of lncRNA ANRIL inhibits proliferation, induces apoptosis, and enhances radiosensitivity in nasopharyngeal carcinoma cells through regulating miR-125a. Cancer Biol Ther 18(5):331–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jiang H et al (2017) Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression. Radiat Oncol 12(1):65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xue Y et al (2017) LncRNA GAS5 inhibits tumorigenesis and enhances radiosensitivity by suppressing miR-135b expression in non-small cell lung cancer. Oncol Res 25(8):1305

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Changyu Sun.

Ethics declarations

Conflict of interest

The authors declare no competing or financial interests.

Ethical approval

This study was approved by the Ethics Committee of Zhengzhou University and written informed consent was obtained for the use of tissue samples from all participants enrolled in this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, Y., He, P., Xie, X. et al. Knockdown of SUMO1P3 represses tumor growth and invasion and enhances radiosensitivity in hepatocellular carcinoma. Mol Cell Biochem 450, 125–134 (2019). https://doi.org/10.1007/s11010-018-3379-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-018-3379-8

Keywords

Navigation