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LINC00657 knockdown suppresses hepatocellular carcinoma progression by sponging miR-424 to regulate PD-L1 expression

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Abstract

Background

Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed malignant tumor and the fourth leading cause of cancer-related deaths worldwide. As a novel non-coding RNA, LINC00657 was firstly identified as an oncogenic role in breast cancer. However, few research focus on the effect of LINC00657 on the progression of HCC.

Objectives

The purpose of this study was to investigate the effect of LINC00657 on HCC tissues and cells, and further explore the potential mechanism.

Methods

We first measured the expression of LINC00657 in HCC tissues and cell lines using qRT-PCR. Next we established LINC00657 knockdown in HCC cells. CCK-8 assay, cell invasion assay, flow cytometry analysis, qRT-PCR and western blotting were applied to assess the role of LINC00657 knockdown in the biological behavior of HCC cells. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism.

Results

LINC00657 was remarkably overexpressed in HCC tissues and cell lines, associated with poor prognosis. LINC00657 knockdown repressed cell proliferation and invasion, promoted cell apoptosis of HCC cell lines. The bioinformatics analysis showed LINC00657 sponged miR-424 as a ceRNA. Besides, PD-L1 mimic rescued the suppression of si-LINC00657 in the biological behavior of HCC cells.

Conclusion

In a word, we observed LINC00657 regulated PD-L1 expression by sponging miR-424, thus affecting the developments of hepatocellular carcinoma. These findings LINC00657 may provide new evidence for therapeutic application in hepatocellular carcinoma.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

References

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  • Chen S, Wang RX, Liu Y, Yang WT, Shao ZM (2017) PD-L1 expression of the residual tumor serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy. Int J Cancer 140:1384–1395

    Article  CAS  Google Scholar 

  • Chu L, Yu L, Liu J, Song S, Yang H, Han F, Liu F, Hu Y (2019) Long intergenic non-coding LINC00657 regulates tumorigenesis of glioblastoma by acting as a molecular sponge of miR-190a-3p. Aging (Albany NY) 11:1456–1470

    Article  CAS  Google Scholar 

  • Fang Y, Liang X, Xu J, Cai X (2018) miR-424 targets AKT3 and PSAT1 and has a tumor-suppressive role in human colorectal cancer. Cancer Manag Res 10:6537–6547

    Article  CAS  Google Scholar 

  • Feng RM, Zong YN, Cao SM, Xu RH (2019) Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond) 39:22

    Article  Google Scholar 

  • Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9:703–719

    Article  CAS  Google Scholar 

  • He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  CAS  Google Scholar 

  • Jin C, Li M, Ouyang Y, Tan Z, Jiang Y (2017) MiR-424 functions as a tumor suppressor in glioma cells and is down-regulated by DNA methylation. J Neurooncol 133:247–255

    Article  CAS  Google Scholar 

  • Koirala P, Roth ME, Gill J, Piperdi S, Chinai JM, Geller DS, Hoang BH, Park A, Fremed MA, Zang X et al (2016) Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. Sci Rep 6:30093

    Article  CAS  Google Scholar 

  • Kung JT, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193:651–669

    Article  CAS  Google Scholar 

  • Lei Y, Wang YH, Wang XF, Bai J (2018) LINC00657 promotes the development of colon cancer by activating PI3K/AKT pathway. Eur Rev Med Pharmacol Sci 22:6315–6323

    CAS  PubMed  Google Scholar 

  • Munn DH, Bronte V (2016) Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol 39:1–6

    Article  CAS  Google Scholar 

  • Peng W, Fan H (2016) Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway. Biomed Pharmacother 83:450–455

    Article  CAS  Google Scholar 

  • Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  CAS  Google Scholar 

  • Rafiee A, Riazi-Rad F, Havaskary M, Nuri F (2018) Long noncoding RNAs: regulation, function and cancer. Biotechnol Genet Eng Rev 34:153–180

    Article  CAS  Google Scholar 

  • Sia D, Villanueva A, Friedman SL, Llovet JM (2017) Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology 152:745–761

    Article  CAS  Google Scholar 

  • Sun W, Yang Y, Xu C, Guo J (2017) Regulatory mechanisms of long noncoding RNAs on gene expression in cancers. Cancer Genet 216–217:105–110

    Article  Google Scholar 

  • Tatli Dogan H, Kiran M, Bilgin B, Kilicarslan A, Sendur MAN, Yalcin B, Ardicoglu A, Atmaca AF, Gumuskaya B (2018) Prognostic significance of the programmed death ligand 1 expression in clear cell renal cell carcinoma and correlation with the tumor microenvironment and hypoxia-inducible factor expression. Diagn Pathol 13:60

    Article  Google Scholar 

  • Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–352

    Article  CAS  Google Scholar 

  • Tovoli F, Negrini G, Benevento F, Faggiano C, Goio E, Granito A (2018) Systemic treatments for hepatocellular carcinoma: challenges and future perspectives. Hepat Oncol 5:HEP01

    Article  Google Scholar 

  • Wang YG, Wang T, Shi M, Zhai B (2019) Long noncoding RNA EPB41L4A-AS2 inhibits hepatocellular carcinoma development by sponging miR-301a-5p and targeting FOXL1. J Exp Clin Cancer Res 38:153

    Article  Google Scholar 

  • Wu X, Ruan Y, Jiang H, Xu C (2017) MicroRNA-424 inhibits cell migration, invasion, and epithelial mesenchymal transition by downregulating doublecortin-like kinase 1 in ovarian clear cell carcinoma. Int J Biochem Cell Biol 85:66–74

    Article  CAS  Google Scholar 

  • Yu WB, Rao A, Vu V, Xu L, Rao JY, Wu JX (2017) Management of centrally located hepatocellular carcinoma: update 2016. World J Hepatol 9:627–634

    Article  Google Scholar 

  • Zhang R, Niu Z, Pei H, Peng Z (2020) Long noncoding RNA LINC00657 induced by SP1 contributes to the non-small cell lung cancer progression through targeting miR-26b-5p/COMMD8 axis. J Cell Physiol 235:3340–3349

    Article  CAS  Google Scholar 

  • Zhao X, Liu Y, Yu S (2017) Long noncoding RNA AWPPH promotes hepatocellular carcinoma progression through YBX1 and serves as a prognostic biomarker. Biochim Biophys Acta Mol Basis Dis 1863:1805–1816

    Article  CAS  Google Scholar 

  • Zhu RX, Seto WK, Lai CL, Yuen MF (2016) Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region. Gut Liver 10:332–339

    Article  Google Scholar 

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Acknowledgement

In compliance with the ethics committee of the First Affiliated Hospital of Xinjiang Medical University, all patients provided written consent for the use of their tissues in this study.

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Authors and Affiliations

  1. Department of Liver & Laparoscopic Surgery, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan South Road, Xinshi District, Ürümqi, 830054, Xinjiang Uyghur Autonomous Region, China

    Xinling Cao, Tao Li, Chengming Zhou, Lei Bai, Jinming Zhao & Turgunjan Tursun

  2. Department of Proctology, Xinjiang General Hospital of People’s Liberation Army, Ürümqi, 830000, Xinjiang Uyghur Autonomous Region, China

    Guanping Zhang

Authors
  1. Xinling Cao
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  2. Guanping Zhang
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  3. Tao Li
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  4. Chengming Zhou
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  5. Lei Bai
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  6. Jinming Zhao
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  7. Turgunjan Tursun
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Contributions

TT designed experiments; XLC, GPZ and TL performed experiments; CGZ and LB analyzed the data; JMZ wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Turgunjan Tursun.

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Conflict of interest

Xinling Cao, Guanping Zhang, Tao Li, Chengming Zhou, Lei Bai, Jinming Zhao and Turgunjan Tursun declare that they have no conflict of interest.

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Cao, X., Zhang, G., Li, T. et al. LINC00657 knockdown suppresses hepatocellular carcinoma progression by sponging miR-424 to regulate PD-L1 expression. Genes Genom 42, 1361–1368 (2020). https://doi.org/10.1007/s13258-020-01001-y

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  • DOI: https://doi.org/10.1007/s13258-020-01001-y

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