Introduction:
An altered regulation of long non-coding RNAs (lncRNA), that modify important cell-specific,
molecular processes, is described in oncogenesis. Since only few is known about lncRNAs
in squamous cell carcinomas (SCC) of the head and neck (HN), we want to identify and
functionally characterize relevant lncRNAs in HNSCC.
Methods:
A combined research of the TANRIC database and literature identified CASC9 and HOTAIR
as promising candidates. Therefore, an expression analysis by RT-qPCR was performed
in 21 HNSCC-cell lines and in 98 HNSCC + 68 control specimen. For functional analysis,
CASC9 was overexpressed using lentiviral vector transduction in low CASC9 expressing
cell lines (HaCaT, FADU) and CASC9 expression was downregulated by shRNA in an CASC9
overexpressing cell line (UMSCC 14A). Proliferation and clonogenity were measured
by colony building assays, chemosensitivität by MTT-Assay and migration by Ibidi-wound
healing assay.
Results:
A marked overexpression of both lncRNAs was found in most tumor specimen and in 17
of 21 HNSCC cell lines. A combined expression analysis of both lncRNAs improved specifity
of tumor detection. A clear overexpression of CASC9 also characterized PEC of other
organs (bladder, cervix, lung, uterus) while a low expression was seen in prostate,
renal and thyroid cancer. An influence of CASC9 regulation on proliferation, migration
and clonogenity in HNSCC-cell lines could not be detected.
Conclusion:
The lncRNAs CASC9 and HOTAIR are specifically and clearly overexpressed in squamous
cell carcinomas. Thus, they provide excellent biomarkers for these cancers.
