Abstract
Long noncoding RNAs (lncRNAs), such as LINC00462, HOTAIR, and MALAT1, are significantly upregulated in hepatocellular carcinoma (HCC) tissues. However, lncRNA expression in the serum of HCC patients is still unclear. To identify candidate lncRNAs for HCC diagnosis, we purified exosomal total RNA from the serum of healthy volunteers (controls) and hepatitis, cirrhosis, and HCC patients. To assess the function of lncRNAs, small interfering RNAs and overexpression vectors were designed and cell viability and cell apoptosis assays conducted. The exosomes of the control group had a larger number of lncRNAs with a high amount of alternative splicing compared to hepatic disease patients. qPCR assays showed that lnc-FAM72D-3, lnc-GPR89B-15, lncZEB2-19, and lnc-EPC1-4 are differentially expressed in HCC. Furthermore, the expression level of lnc-EPC1-4 correlated with age. While the expression levels of lnc-GPR89B-15 and lnc-EPC1-4 correlated with serum alpha-fetoprotein level. lnc-FAM72D-3 knockdown decreased cell viability and promoted cell apoptosis, indicating that lnc-FAM72D-3 functions as an oncogene in HCC. In contrast, lnc-EPC1-4 overexpression inhibited cell proliferation and induced cell apoptosis, indicating that it functions as a tumor suppressor gene. Collectively, these findings show that lnc-FAM72D-3 and lnc-EPC1-4 play a novel role that might contribute to hepatocarcinogenesis and identify potential candidate biomarkers for HCC diagnosis.
Highlights
Liver cancer, called hepatocellular carcinoma (HCC), is the fifth-most common cancer worldwide, with a mortality rate that increased by almost 3% per year from 2010 to 2014 [1, 2]
16 12 17 increased apoptosis (Figure 7C, 7D). These results indicated that lnc-FAM72D-3 functions as an oncogene that is upregulated in HCC, while lnc-EPC1-4 functions as a tumor suppressor gene that is downregulated in HCC
We examined exosomal Long noncoding RNAs (lncRNAs) that are differentially expressed in hepatic disease patients
Summary
Called hepatocellular carcinoma (HCC), is the fifth-most common cancer worldwide, with a mortality rate that increased by almost 3% per year from 2010 to 2014 [1, 2]. Most HCC patients present with intra- and extrahepatic metastasis upon diagnosis, which limits their treatment options to radiotherapy and chemotherapy. The treatment efficacy of radiotherapy and chemotherapy is limited [3]. Early diagnosis of HCC is of utmost importance. The most commonly used methods of diagnosing HCC involve imaging or detection of tumor biomarkers, such as alpha-fetoprotein (AFP), from the patient’s serum. These techniques are less www.aging-us.com sensitive for early diagnosis of HCC [4].
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