lnc‐HOTAIR predicts hepatocellular carcinoma in chronic hepatitis C genotype 4 following direct‐acting antivirals therapy

Abstract

Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cutoff value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.

Progress of HOTAIR-microRNA in hepatocellular carcinoma

“…HOTAIR, as a kind of lncRNA, is a 2158 bp RNA and located on chromosome 12 [ 6 , 8 ]. HOTAIR is the first lncRNA found to have reverse transcription effect, which plays a role in many diseases, such as tumor, rheumatoid arthritis, heart disease and so on [ 9 – 11 ]. HOTAIR has been proved to be highly expressed in many cancers and regarded as a tumor gene [ 12 ].…”

“…However, the high expression of HOTAIR can promote the recurrence and metastasis of hepatocellular carcinoma, affect the prognosis of patients and shorten the survival time of patients [ 13 ]. Therefore, HOTAIR has been regarded as a new tumor marker of HCC [ 9 , 14 , 15 ].…”

LncRNA: A Potential Target for Host-Directed Therapy of Candida Infection

“…HOTAIR could also upregulate the TNF-α levels by modifying the p65 subunit at the posttranslational level [ 147 ]. Interestingly, in HCV-4 patients, HOTAIR could serve as a risk assessment biomarker following direct-acting antiviral therapy [ 148 ], suggesting that HOTAIR has potential as a biomarker for the treatment or risk evaluation of infectious diseases.…”

LncRNAs as Therapeutic Targets and Potential Biomarkers for Lipid-Related Diseases

“…In addition, small molecules were screened to modulate the lncRNA HOX transcript antisense RNA ( HOTAIR )-enhancer of zeste homolog2 (EZH2) interaction using alphaScreen technology ( Pedram Fatemi et al, 2015 ). The interaction was inhibited with HOTAIR-polycomb repressive complex 2 (PRC2) binding through small-molecule intervention resulting in reduced metastatic phenotypes in many cancers, including breast ( Gupta et al, 2010 ), colorectal ( Kogo et al, 2011 ), and hepatocellular carcinomas ( El-Khazragy et al, 2020 ). However, it is necessary to investigate the lncRNA-protein interaction and pharmacological trends further to develop more effective small molecule drugs ( Figure 3 ).…”