Through the modulation of miR-211-5p and NR1I3, long noncoding RNAs (lncRNAs) work to regulate the progression of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by interfering with the cellular physiology of HCC, according to research published in the Journal of Cellular and Molecular Medicine.

Researchers sought to investigate the mechanism of lncRNA F11-AS1 in HBV-related HCC and proposed that interactions along the lncRNA F11-AS1/miR-211-5p/NR1I3 axis may be involved in the development of tumors in HBV-related HCC. Both HCC and normal adjacent tissues were collected from a patient population diagnosed with HCC between 2010 and 2013. The total study population included 73 patients, 45 of whom were HBV positive and 28 of whom were HBV negative (HBV+ and HBV-).

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All tissue samples underwent reverse transcription-quantitative polymerase chain reaction assay testing to determine lncRNA F11-AS1 expression, with a differential analysis of the expression performed in HBV+ and HBV- tissues. The results indicated that there were no significant differences in lncRNA F11-AS1 expression between HBV- HCC tissues and corresponding adjacent tissues. Conversely, HBV+ HCC tissues had lower lncRNA F11-AS1 expression compared with adjacent tissues.

Using a Kaplan-Meier analysis, investigators analyzed HCC prognosis relative to lncRNA F11-AS1 expression. A higher survival rate was noted in patients with HBV+ HCC with higher lncRNA F11-AS1 expression, compared with those with lower expression.


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Researchers also sought to determine how HBV inhibits the expression of lncRNA F11-AS1 in HCC cells. HepG2.2.15 cells were transfected with HBV-encoded X, C, S, and P plasmid proteins. After extracting the RNA content from the transfected cells, investigators determined lncRNA F11-AS1 expression using a reverse transcription-quantitative polymerase chain reaction assay. In particular, HBx was found to downregulate the expression of lncRNA F11-AS1, although researchers noted that the underlying mechanism behind this warrants further investigation: lncRNA F11-AS1 was also found to upregulate NR1I3 expression through the process of binding to miR-211-5p. According to researchers, this result demonstrated that the lncRNA F11-AS1-impaired miR-211-5p-targeted inhibition of NR1I3 “could impede the proliferation, apoptosis, migration, and invasion” of HepG2.2.15 cells, ultimately preventing the development and progression of HBV-related HCC.

“The regulation of lncRNA F11-AS1/miR-211-5p/NR1I3 axis in HBV-related HCC cell line … was primarily investigated in the current study,” the researchers concluded. “However, the clinical efficacy and future potential use of the lncRNA F11-AS1/miR-211-5p/NR1I3 axis in treatment of HBV-related HCC warrant further studies to improve the overall outcomes of HCC patients.”

Reference

Deng Y, Wei Z, Huang M, et al. Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulation NR1I3 via binding to microRNA-211-5p [published online December 27, 2019]. J Cell Mol Med. doi: 10.1111/jcmm.14881