• Long non-coding RNAs and circular RNAs as potential biomarkers in hepatocellular carcinoma: A review study
  • Mohammad Hossein Donyavi,1 Sadra Salehi-Mazandarani,2 Parvaneh Nikpour,3,*
    1. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
    2. Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
    3. Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


  • Introduction: Liver cancer is the sixth most common cancer in the world. Based on estimations, more than one million people will be diagnosed with liver cancer annually, by 2025. Hepatocellular carcinoma (HCC) accounts for > 90% of liver cancer patients. Since most of the HCC patients are diagnosed at advanced stages, the disease becomes incurable with poor prognosis. Therefore, new prognostic and diagnostic biomarkers for HCC are needed. Up to now, different types of RNAs have been identified to be dysregulated in cancers indicating their important roles. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are two types of most commonly studied RNAs. LncRNAs are a group of non-coding RNAs with a length of > 200 nucleotides. They have roles in different cellular processes such as chromosome remodeling, transcription and intracellular trafficking. Abnormal expression of lncRNAs correlate with progression of cancer, tumorigenesis and metastasis. CircRNAs are a type of endogenous RNAs with single-stranded covalently closed loop structure without 5́ and 3́ free ends. Due to this closed structure, they are resistant to exonucleases. They can function as microRNA sponges, protein scaffolds and modulators of transcription. Studies revealed that both lncRNAs and circRNAs are differentially expressed and can utilized as prognostic and diagnostic biomarkers in HCC. In this study, we investigated these two RNA types as potential biomarkers in HCC.
  • Methods: In the current study, we searched in PubMed and Google Scholar to find relevant and the newest review and original articles regarding the subject and aim of the study.
  • Results: HCC is a global health challenge, therefore novel biomarkers to diagnose the disease at early stages and predict the prognosis of patients are needed. LncRNAs could be utilized as potential prognostic and diagnostic biomarkers and therapeutic targets in cancer. Various studies have indicated momentous lncRNAs in HCC. For instance, overexpression of HOTTIP, SNHG3 and FOXD2-AS1, and decreased expression of ELMO1-AS1 and NKILA as prognostic biomarkers represent poor prognosis of HCC patients. Several studies show the importance of exosome-derived lncRNAs as candidate biomarkers in HCC. For example, the exosomal expression of three lncRNAs; ENSG00000248932.1, ENST00000440688.1 and ENST00000457302.2, as potential biomarkers, increase in HCC patients comparing with both chronic hepatitis patients and healthy volunteers. SPRY4-IT1, Linc00152 and UCA1, which have overexpressed in serum of HCC patients, can be mentioned as proper diagnostic biomarkers. One of the most studied lncRNA in HCC is HULC which is indicated as a strong diagnostic biomarker for HCC. This lncRNA is overexpressed in serum, exosomes and HCC tissues. CircRNAs have outstanding specialties including high stability and tissue-specific and developmental stage-specific expression patterns, and could be served as promising biomarkers in cancer. Studies have identified important circRNAs in HCC. For example, increased expression of circRHOT1, SCD-circRNA 2 and hsa_circ_104348, and decreased expression of circTRIM33-12 and circDLC1, as prognostic biomarkers, can predict poor prognosis of HCC patients. On the other hand, circRNAs as diagnostic biomarkers have been reported. Exosomal expression of hsa_circ_0004277 which is significantly increased in the plasma of HCC patients, has diagnostic value. Furthermore, hsa_circ_0004001, hsa_circ_0004123 and hsa_circ_0075792, which have increased expression in the HCC patient blood samples compared to healthy controls, separately or in a combination (with higher sensitivity and specificity), could be used as valuable diagnostic biomarkers. These studies have unveiled important lncRNAs and circRNAs which can be utilized as potential biomarkers for HCC in the near future.
  • Conclusion: long non-coding RNAs and circular RNAs could be served as novel prognostic and diagnostic biomarkers in HCC. In the current study, we tried to present a useful brief regarding these two RNA types as promising biomarkers in HCC.
  • Keywords: Hepatocellular carcinoma, Long non-coding RNAs, Circular RNAs, Biomarker