Abstract 42P
Background
Hepatocellular carcinoma (HCC) is one of the most fatal solid malignancies. Recently, the emergence of immune checkpoint inhibitor (ICI) has revolutionized HCC therapeutic regimens. Galectins (Gal-) 1,3,9 have been casted as recent immune checkpoints. Yet, HCC tumors is highly packed with immunosuppressive mediators such as Interleukins (IL-),6,10 that act as formidable barrier for any immune cell to attack the tumor. Long non-coding RNAs (LncRNAs) is a new class of ncRNAs that possess the capability to influence various facets of the tumor microenvironment (TME). LncRNAs have been found to modulate the expression of immune checkpoint molecules on tumor cells, potentially impeding the therapeutic effectiveness of ICIs. Therefore, this renders them as potential cancer-immune biomarkers for diagnosis, prognosis, and therapeutic regimen determinants. sONE and MEG3 are tumor suppressor lncRNAs in several malignant contexts. However, thier role in HCC and its TME has been rarely investigated. The aim of this study is to unravel the immunomodulatory role of sONE and MEG3 in HCC through investigating their interaction with several immune targets.
Methods
HCV-induced HCC tissues and their respective normal counterparts were collected (n=25). HCC cell lines were cultured and transfected with sONE and MEG3 siRNAs. Total RNA was extracted and quantified by qRT-PCR. IL-10, IL-6, and NO in cellular supernatant was measured using ELISA kits and Greiss Assay. HCC hallmarks were assessed using MTT, BrdU, colony forming assay.
Results
sONE and MEG3 lncRNAs are downregulated while miR-155, Gal-1,3,9, IL-6 and Il-10 are markedly upregulated in HCC tissues. Upon knocking down of either sONE or MEG3 in Huh7 and HepG2 cells, a marked repression of HCC hallmarks was observed on the cellular viability, proliferation and clonogenicity levels. On the molecular level, sONE and MEG3 were found to sponge the oncomiR-155 in HCC cells. On the immunological level, sONE and MEG3 siRNAs resulted in a marked induction of immune suppressive markers Gal-1,3,9 and cytokines IL-6, IL-10 and NO.
Conclusions
sONE and MEG3 are novel tumor suppressor immuno-activator lncRNAs in HCC through harnessing miR-155 onocgenic roles and inducing its immunomodulatory role.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.