Long non-coding RNAs (CASC2 and TUG1) in hepatocellular carcinoma: Clinical significance.

The biology of hepatocellular carcinoma remains poorly understood. Long non-coding RNAs (lncRNAs) have been confirmed to be key regulators of most cell processes and cancer. The lncRNA cancer susceptibility candidate 2 (CASC2) was originally identified as a downregulated gene in endometrial cancer and acted as a tumor suppressor. The lncRNA taurine up-regulated gene 1 (TUG1) has been shown to play an oncogenic role in various cancers. However, the relative expression of CASC2 and TUG1 in hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) and the relationship between both remains unclear. The present study aimed to evaluate both lncRNA CASC2 and TUG1 relative gene expression in whole blood of HCC/HCV patients in relation to HCV and healthy subjects and to relate them to each other and to different clinicopathological factors. The relative expression of CASC2 and TUG1 was estimated by a quantitative reverse transcriptase-polymerase chain reaction in 30 HCC/HCV patients and compared with 20 cases of HCV patients and 20 controls. CASC2 was downregulated in HCC/HCV patients, whereas TUG1 was overexpressed in relation to HCV and the control group, indicating their antagonistic effect. This suggests their role in the pathogenesis of HCC on top of HCV. Their expression was correlated to Barcelona Clinic Liver Cancer stage and serum alpha-fetoprotein level. CASC2 and TUG1 could be new potential biomarkers with a valid non-invasive technique.

Refai NS ，Louka ML ，Halim HY ，Montasser I ... -  《-》

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Golam RM ，Khalil MAF ，Shaker OG ，Ahmed TI ，Elguaad MKA ，Hassan EA ，El-Ansary MRM ，Ismail A ，Kandil YI ，Mohammed OA ，Doghish AS ... -  《PLoS One》

Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2.

Huang MD ，Chen WM ，Qi FZ ，Sun M ，Xu TP ，Ma P ，Shu YQ ... -  《Molecular Cancer》

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

Gan Y ，Han N ，He X ，Yu J ，Zhang M ，Zhou Y ，Liang H ，Deng J ，Zheng Y ，Ge W ，Long Z ，Xu X ... -  《-》

Serum expression and diagnostic potential of long non-coding RNAs NEAT1 and TUG1 in viral hepatitis C and viral hepatitis C-associated hepatocellular carcinoma.

The present study investigated the serum detectability and the diagnostic implications of long non-coding RNAs; nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) in viral hepatitis C (HCV) and HCV-associated hepatocellular carcinoma (HCC). The study included twenty healthy controls, forty non-malignant HCV patients and forty HCV-associated HCC patients. The study assessed liver function tests, the antioxidant status, serum alpha fetoprotein, p53, NEAT1 and TUG1. Diminished serum expression of NEAT1 and TUG1 was observed in HCV and HCV-associated HCC and was closely associated with deregulated liver function and elevated AFP levels. A model of NEAT1, TUG1 and AFP accurately differentiated between HCC patients and healthy controls with sensitivity greater than that of AFP alone. Additionally, the diagnostic performance of a model of TUG1, p53 and AFP was superior to that of each marker alone for predicting HCC in HCV patients. Significant alterations in the serum expression of NEAT1 and TUG1 in HCV and HCV-associated HCC patients were recorded. We propose NEAT1 and TUG1 as non-invasive, cost-effective and complementary biomarkers that improve the diagnostic characteristics of AFP.

Mohyeldeen M ，Ibrahim S ，Shaker O ，Helmy H ... -  《-》