We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

RNA sequencing identifies two novel liver-specific long noncoding RNAs with potential diagnostic value in hepatocellular carcinoma

    Chao Tan‡

    Department of Epidemiology & Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    Department of Epidemiology & Health Statistics, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541100, PR China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Xi Zeng‡

    Department of Occupational & Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    Department of Occupational & Environmental Health, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541100, PR China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Meile Mo

    Department of Epidemiology & Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    ,
    Xiaoyun Ma

    Department of Epidemiology & Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    ,
    Qiuli Liang

    Department of Epidemiology & Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    ,
    Wenjie Liang

    Department of Social Medicine, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    ,
    Wenxiu Huang

    Department of Occupational & Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    ,
    Ke Wang

    Department of Occupational & Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    ,
    Li Yang

    **Author for correspondence:

    E-mail Address: yangli8290@hotmail.com

    Department of Occupational & Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    &
    Xiaoqiang Qiu

    *Author for correspondence:

    E-mail Address: xqqiu9999@163.com

    Department of Epidemiology & Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, PR China

    Published Online:https://doi.org/10.2217/bmm-2020-0825

    Aim: To explore the expression profiles of long noncoding RNAs (lncRNAs) and identify novel lncRNAs as biomarkers for early diagnosis and therapy of hepatocellular carcinoma (HCC). Materials & methods: Expression profiles of lncRNAs and mRNAs in five paired HCC and adjacent normal tissues were obtained by RNA sequencing. Eight lncRNAs, including two novel liver-specific lncRNAs (NONHSAT059247.2 and NONHSAT013897.2), were validated in another 74 pairs of HCC and adjacent normal tissues by quantitative reverse transcription PCR. Results: The results of quantitative reverse transcription PCR showed that NONHSAT252133.1, NONHSAT112116.2 and NONHSAT242657.1 were significantly upregulated in HCC tissues, whereas NONHSAT169790.1, NONHSAT059247.2 and NONHSAT013897.2 were significantly downregulated. Two liver-specific lncRNAs demonstrated excellent diagnostic performance: NONHSAT059247.2 (area under the curve = 0.941, 95% CI: 0.902–0.979, p < 0.0001), NONHSAT013897.2 (area under the curve = 0.944, 95% CI: 0.906–0.983, p < 0.0001). Conclusion: The liver-specific lncRNAs NONHSAT059247.2 and NONHSAT013897.2, may provide new biomarkers for the future study on diagnosis, therapy and mechanisms of HCC.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68(6), 394–424 (2018).
    • 2. Kulik L, El-Serag HB. Epidemiology and management of hepatocellular carcinoma. Gastroenterology 156(2), 477–491 (2019).
    • 3. Choi DT, Davila JA, Sansgiry S et al. Factors associated with delay of diagnosis of hepatocellular carcinoma in patients with cirrhosis. Clin. Gastroenterol. Hepatol. doi:10.1016/j.cgh.2020.07.026 (2020) (Online ahead of print). • Shows that the diagnosis of hepatocellular carcinoma was delayed in a large proportion of patients with cirrhosis and explained the reasons for the delay.
    • 4. Zhang J, Li Z, Liu L et al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology 67(1), 171–187 (2018). • A typical study that identifies that a long noncoding RNA (lncRNA) TSLNC8 plays an important role in hepatocellular carcinoma through a mechanism of binding to a protein and regulating its function.
    • 5. Chen DL, Lu YX, Zhang JX et al. Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression. Theranostics 7(19), 4836–4849 (2017). • Founds that a lncRNA UICLM promoted colorectal cancer liver metastasis by a common mechanism of acting as a competing endogenous RNA.
    • 6. Wong CM, Tsang FH, Ng IO. Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications. Nat. Rev. Gastroenterol. Hepatol. 15(3), 137–151 (2018).
    • 7. Huarte M. The emerging role of lncRNAs in cancer. Nat. Med. 21(11), 1253–1261 (2015). •• Emphasizes the important clinical value of tissue-specific expressed lncRNAs.
    • 8. He J, Zuo Q, Hu B et al. A novel, liver-specific long noncoding RNA LINC01093 suppresses HCC progression by interaction with IGF2BP1 to facilitate decay of GLI1 mRNA. Cancer Lett. 450, 98–109 (2019).
    • 9. Mo M, Liu S, Ma X et al. A liver-specific lncRNA, FAM99B, suppresses hepatocellular carcinoma progression through inhibition of cell proliferation, migration, and invasion. J. Cancer Res. Clin. Oncol. 145(8), 2027–2038 (2019).
    • 10. Ma X, Mo M, Tan HJJ et al. LINC02499, a novel liver-specific long non-coding RNA with potential diagnostic and prognostic value, inhibits hepatocellular carcinoma cell proliferation, migration, and invasion. Hepatol. Res. 50(6), 726–740 (2020).
    • 11. Zeng YL, Guo ZY, Su HZ et al. Diagnostic and prognostic value of lncRNA cancer susceptibility candidate 9 in hepatocellular carcinoma. World J. Gastroenterol. 25(48), 6902–6915 (2019).
    • 12. Chao Y, Zhou D. lncRNA-D16366 is a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma. Med. Sci. Monit. 25, 6581–6586 (2019).
    • 13. Sasaki R, Kanda T, Yokosuka O et al. Exosomes and hepatocellular carcinoma: from bench to bedside. Int. J. Mol. Sci. 20(6), 1406 (2019).
    • 14. Lv B, Zhang L, Miao R et al. Comprehensive analysis and experimental verification of LINC01314 as a tumor suppressor in hepatoblastoma. Biomed. Pharmacother. 98, 783–792 (2018).
    • 15. Lim LJ, Wong SYS, Huang F et al. Roles and regulation of long noncoding RNAs in hepatocellular carcinoma. Cancer Res. 79(20), 5131–5139 (2019).
    • 16. He Y, Meng XM, Huang C et al. Long noncoding RNAs: novel insights into hepatocelluar carcinoma. Cancer Lett. 344(1), 20–27 (2014).
    • 17. Fan H, Lv P, Mu T et al. LncRNA n335586/miR-924/CKMT1A axis contributes to cell migration and invasion in hepatocellular carcinoma cells. Cancer Lett. 429, 89–99 (2018).
    • 18. Zhou Y, Huan L, Wu Y et al. LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma. Cancer Lett. 469, 399–409 (2020).
    • 19. Wang Y, He L, Du Y et al. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell 16(4), 413–425 (2015).
    • 20. Pan W, Li W, Zhao J et al. lncRNA-PDPK2P promotes hepatocellular carcinoma progression through the PDK1/AKT/Caspase 3 pathway. Mol. Oncol. 13(10), 2246–2258 (2019).
    • 21. Sun L, Wang L, Chen T et al. microRNA-1914, which is regulated by lncRNA DUXAP10, inhibits cell proliferation by targeting the GPR39-mediated PI3K/AKT/mTOR pathway in HCC. J. Cell. Mol. Med. 23(12), 8292–8304 (2019).
    • 22. Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-κB signaling pathways. Nat. Immunol. 12(8), 695–708 (2011).
    • 23. Fan Y, Mao R, Yang J. NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell 4(3), 176–185 (2013).
    • 24. Oeckinghaus A, Ghosh S. The NF-κB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol. 1(4), a000034 (2009).
    • 25. Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat. Rev. Immunol. 18(5), 309–324 (2018).
    • 26. Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding RNA. Nat. Rev. Mol. Cell Biol. 19(3), 143–157 (2018).
    • 27. Cheng D, Deng J, Zhang B et al. LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation. EBioMedicine 36, 159–170 (2018). •• Proposes the expression of lncRNAs in various tissues is more tissue-specific than the coding RNAs, implying their important role in tissues.