New LncRNAs in Chronic Hepatitis C progression: from fibrosis to hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world, and about 80% of the cases are associated with hepatitis B or C. Genetic and epigenetic alterations are accumulated over decades of chronic injury and may affect the functioning of tumor suppressor genes and protooncogenes. Studies have evidenced the role of Long non-coding RNAs (LncRNA) with oncogenic or tumor suppressor activities, suggesting a great potential in the treatment, diagnosis or indicator of prognosis in cancer. In this context, the aim of this study was to evaluate the global expression profile lncRNA in hepatic tissue samples with different stages of fibrosis associated with chronic hepatitis C, HCC and normal liver, in order to identify new lncRNAs that could contribute to study the progression of hepatic fibrosis to HCC associated with chronic hepatitis C. RNA-Seq was performed on Illumina NextSeq platform to identify lncRNAs expressed differently in 15 patients with chronic hepatitis C, three patients with HCC and three normal liver specimens. When the pathological tissues (fibrosis and carcinoma) were compared to normal hepatic tissue, were identified 2, 6 e 34 differentially expressed lncRNAs in moderate fibrosis, advanced fibrosis and HCC, respectively. The carcinoma group had the highest proportion of differentially expressed lncRNA (34) and of these, 29 were exclusive in this type of tissue. A heat map of the deregulated lncRNA revealed different expression patterns along the progression of fibrosis to HCC. The results showed the deregulation of some lncRNA already classified as tumor suppressors in HCC and other cancers, as well as some unpublished lncRNA whose function is unknown. Some of these lncRNAs are dysregulated since the early stages of liver injury in patients with hepatitis C, others overexpressed only in tumor tissue, indicating themselves as candidates of markers of fibrosis progression or tumor, with potential clinical applications in prognosis as well as a therapeutic target. Although there are already studies on lncRNA in hepatocellular carcinoma, this is the first study conducted in samples exclusively of HCV-related liver and HCV HCC. Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the third leading cause of cancer-related death in the world 1. Surgical resection and liver transplantation are the main resources for treatment. However, the results are limited, and the prognosis is poor due to late diagnosis, distant metastases and high risk of postoperative recurrence 2-4. Due to unspecific or absent symptoms in HCC, early detection requires the biannual monitoring of individuals at risk through ultrasound with or without assessment of the alpha-fetoprotein (AFP) biomarker 5. Environmental and genetic factors are involved in hepatic carcinogenesis. About 80% of the cases are associated with hepatitis B or C 6,7 , mainly due to the development of cirrhosis after years of chronic infection 4. Despite advances in the diagnosis and treatment of hepatitis ...

Particulate matter impairs immune system function by up-regulating inflammatory pathways and decreasing pathogen response gene expression

“…mRNA libraries were sequenced with a sequencing depth of at least 20 million reads per sample. RNAseq data were analyzed as described before 57 . Then genes were considered differentially expressed if there was an absolute value of log 2 fold change ≥ 1; and the FDR ≤ 0.05.…”

Dual roles and potential applications of exosomes in HCV infections

“…lncRNAs are transcripts that do not encode proteins but can interact with other molecules, including proteins, DNA, and RNA ( Ferrasi et al, 2020 ). The differential expression of lncRNAs has been identified in HCV infections.…”

HCV and tumor-initiating stem-like cells

“…Due to this review being focused on TICs, more details about TICs and non-coding RNAs are described (such as ( Huang et al, 2018 ; Machida, 2020 ; Rojas et al, 2022 ): More details about TICs and non-coding RNAs are included such as: ( Huang et al, 2018 ; Machida, 2020 ; Rojas et al, 2022 ). In Table 1 HCV-associated HCC are involved in alterations of lncRNAs [( Hou and Bonkovsky, 2013 ; Lange et al, 2013 ; Zhang et al, 2015 ; Zhang et al, 2016 ; Fu et al, 2016 ; Shi et al, 2016 ; Hai et al, 2017 ; Wong et al, 2018 ; Sur et al, 2018 ; Toraih et al, 2018 ; Wang et al, 2018 ; Zhang et al, 2018 ; Cheng et al, 2019 ; Refai et al, 2019 ; Wang et al, 2019 ; Wu et al, 2019 ; Yang et al, 2019 ; Zhao et al, 2019 ; Zheng et al, 2019 ; Zhong et al, 2019 ; El-Khazragy et al, 2020 ; Ferrasi et al, 2020 ; Lorini et al, 2020 ; Machida, 2020 ; Mohyeldeen et al, 2020 ; Morishita et al, 2020 ; Oura et al, 2020 ; Unfried and Fortes, 2020 ; Jing et al, 2021 ; Sabry et al, 2021 ; Wong and Wong, 2021 ; Yao et al, 2021 ; Wang et al, 2022 ; Wei et al, 2022 )]. Upregulated lncRNAs include NORAD (LINC00657), HCP5, lnc-HOTAIR (HOX antisense intergenic RNA), CASC11, HEIM, eosinophil granule ontogeny transcript (EGOT), lncRNA SEMA3B-AS1 [SEMA3B Antisense RNA 1 (Head To Head)], TPT-1S, LINC01189.…”