Abstract
It has been reported that long non-coding RNA PANDA was disregulated in varieties types of tumor, but its expression level and biological role in hepatocellular carcinoma (HCC) remains contradictory. We detected PANDA expression in two independent cohorts (48 HCC patients following liver transplantation and 84 HCC patients following liver resection), and found that PANDA was down-regulated in HCC. Thereafter we explored its function in cancer biology by inversing its low expression. Surprisingly, overexpression of PANDA promoted HCC proliferation and carcinogenesis in vitro and in vivo. Mechanistically, PANDA repressed transcriptional activity of senescence associated inflammatory factor IL8, which leaded to inhibition of cellular senescence. Therefore, our research help to better understand the complex role of PANDA in HCC, and suggest more thoughtful strategies should be applied before it can be treated as a potential therapeutic target.
Highlights
The expression levels and biological functions of PANDA in diverse cancers remain contradictory
Puvvula et al.[10] reported that PANDA was low expressed in hepatocellular carcinoma (HCC) compared with normal liver tissues and not associated with p53 mutational status in HCC, Peng et al.[15] uncovered that PANDA was high expressed in HCC tissues and cell lines
To demonstrate whether PANDA was induced by p53-mediated DNA damage in HCC, we treated two liver cancer cell lines HCC-LM3 and Huh[7] with doxorubicin (DOX) at 100 nM and 500 nM for 24 hours, and found that PANDA expression was elevated and had a dose-dependent relation(Fig. 1c)
Summary
The expression levels and biological functions of PANDA in diverse cancers remain contradictory. Puvvula et al.[10] reported that PANDA was significantly reduced in HCC, Peng et al.[15] uncovered that PANDA was overexpressed in HCC These studies indicate that PANDA plays a complicated role in cancers, and its exact expression level and underlying function in HCC need to be further clearly illuminated. We demonstrated that PANDA was significantly lower expressed in HCC tissue, but had a tumor-promoting feature both in vivo and vitro. This aberrant function was attributed to its inhibitory action on cell senescence by suppressing senescence associated inflammatory chemokine IL8
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