Differential expression profiling of long non-coding RNA GAS5 and miR-126-3p in human cancer cells in response to sorafenib

Abstract

Long non-coding RNAs (lncRNAs) and microRNAs are involved in numerous physio-pathological conditions included cancer. To better understand the molecular mechanism of the oral antitumor multikinase inhibitor sorafenib, we profiled the expression of a panel of lncRNAs and miRNAs by qPCR array in a sorafenib-treated hepatocellular carcinoma (HCC) cell line. Among the most affected ncRNAs, we found that sorafenib mediated the dysregulation of the lncRNAs GAS5, HOTTIP and HOXA-AS2 and the miR-126-3p, in a panel of human cancer cell lines (HCC, renal and breast carcinomas). By luciferase gene reporter assay, we discovered that GAS5 may act as a sponge for miR-126-3p in HCC cells. The expression level of GAS5 and miR-126-3p was verified in human liquid and/or solid biopsies from HCC patients. miR-126-3p expression in HCC tissues was decreased respect to their correspondent peritumoral tissues. The levels of plasmatic circulating miR-126-3p and GAS5 were significantly higher and lower in HCC patients compared to healthy subjects, respectively. This study highlighted the capability of sorafenib to modulate the expression of a wide range of ncRNAs and specifically, GAS5 and miR-126-3p were involved in the response to sorafenib of different cancer cell types.

Investigation of the Prognostic Significance of Vasculogenic Mimicry and Its Inhibition by Sorafenib in Canine Mammary Gland Tumors

“…To investigate cell viability after sorafenib treatment, we determined IC 50 values using an MTT assay. Interestingly, the IC 50 values for our CMT cell lines were lower than those previously reported in the literature for different human cancer cells (28)(29)(30)(31). This result reinforces the use of sorafenib in dogs with CMT as a preclinical model for human BC and as a therapeutic option for dogs with relatively aggressive CMT.…”

Our emerging understanding of the roles of long non-coding RNAs in normal liver function, disease, and malignancy

“…GAS5 has been implicated in multiple forms of cancers [158], and is a well-known tumor suppressor gene [159]. However, its multitude of roles in HCC has only recently been investigated [160][161][162]. Wang et.…”

Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

“…This miRNA was down-regulated in HCC tissues compared to levels of peritumoral tissues (HCC average=3.91±0.48 vs RQPT average=5.84±0.51; P-value=0.0074). Moreover, circulating miR-126-3p expression levels were significantly higher in HCC patients compared to control subjects (26.7 vs 26.6 mean expression levels; P-value=0.0002) [66]. In vitro data and in vivo determination lead Authors to hypothesize that a reduction of this miRNA could be predictive of response to sorafenib.…”

“…In fact, 75% of patients with miR423-5p level increase achieved a disease control [65]. Also MiR-126-3p was downregulated after sorafenib treatment in HCC cells lines [66]. So far, Faranda et al determinated expression levels of miR-126-3p in HCC tissues and plasma.…”