RNA interference targeting inhibition of S100A4 suppresses cell growth and promotes apoptosis in human laryngeal carcinoma Hep-2 cells

Abstract

Abstract. S100A4 is a small Ca 2+ binding protein that belongs to the S100 family and is involved in a number of cellular functions, including cell cycle control, proliferation, apoptosis, and has a significant role in angiogenesis and neurite extension. However, the exact function and mechanism of S100A4 in laryngeal carcinogenesis remains to be elucidated. The present study was designed to investigate the potential use of RNA interference to inhibit S100A4 expression and activation, as well as the subsequent effect on human laryngeal cancer cell growth and apoptosis. The present study demonstrated that knockdown of S100A4 decreased the proliferation and growth of the human laryngeal cancer Hep-2 cell line. The percentages of the apoptotic cells were 4.23±1.22, 4.92±1.85 and 11.70±4.02% in the control, negative control and S100A4 short hairpin RNA (shRNA) groups, respectively, indicating significant differences among the different groups. The S100A4-mediated induction of apoptosis was demonstrated to be associated with the activation of caspase-3, caspase-8 and caspase-9. Intratumoral injection of S100A4-shRNA inhibited tumor growth in nude mice. Thus, knockdown of S100A4 inhibited the progression of laryngeal squamous carcinoma, decreased proliferation and promoted apoptosis. S100A4 is a potential candidate for therapeutic targeting of laryngeal carcinoma cells.

Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia

“…We show for the first time that normal CD34 + cells and myeloid differentiated lineages express this protein in the cytosol. Knocking down expression of S100A4 in AML lines results in cell death through induction of apoptosis and hence is an attractive target for cancer therapy particularly in AML given that normal cells would be spared [62]. Increasing evidence suggests that expression and subcellular localization of several S100 proteins is different between physiological and pathological conditions.…”

Retracted: RNA interference‐mediated silencing of S100B improves nerve function recovery and inhibits hippocampal cell apoptosis in rat models of ischemic stroke

“…Results from previous studies indicate that RNA interferencemediated knockdown of S100A4 leads to apoptosis of laryngeal cancer cells. 34 Levine suggested that increased apoptosis in Hep-2 cells transfected with S100A4-RNA interference contributes to the reduction of cell numbers. 35 Previous data demonstrates that S100A4 interacts with the tumor suppressor p53 to affect cell growth and p53dependent apoptosis.…”

“…There is little data demonstrating the function of RNA interference‐mediated silencing of S100B in hippocampal cell apoptosis. Results from previous studies indicate that RNA interference‐mediated knockdown of S100A4 leads to apoptosis of laryngeal cancer cells . Levine suggested that increased apoptosis in Hep‐2 cells transfected with S100A4‐RNA interference contributes to the reduction of cell numbers .…”

Persistent Newcastle disease virus infection in bladder cancer cells is associated with putative pro-survival and anti-viral transcriptomic changes

“…The transcriptome analysis revealed several genes, which are associated with the regulation of cell survival such as S100A4 and SYK, both of which were upregulated in EJ28P. Incidentally, S100A4 expression is positively regulated by the Wnt/β-catenin signalling pathway [ 40 ] to protect cells from pro-apoptotic stimuli [ 41 , 42 ]. It was reported that the knockdown of S100A4 decreased cellular proliferation and promoted apoptosis [ 42 ].…”

“…Incidentally, S100A4 expression is positively regulated by the Wnt/β-catenin signalling pathway [ 40 ] to protect cells from pro-apoptotic stimuli [ 41 , 42 ]. It was reported that the knockdown of S100A4 decreased cellular proliferation and promoted apoptosis [ 42 ]. Meanwhile, the SYK gene was reported to provide pro-survival signals [ 43 ] whereas the inhibition of its protein expression resulted in apoptosis and the suppression of cellular proliferation [ 44 ].…”