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. 2021 Oct;129(5):e12812.
doi: 10.1111/eos.12812. Epub 2021 Jul 8.

Effects of miR-224-5p-enhanced downregulation of pannexin-1 on docetaxel-induced apoptosis in amoeboid-like CD44high oral cancer cells

Sho Yokoyama  1 , Hideo Shigeishi  2 , Hiroshi Murodumi  1 , Miyuki Sakuma  1 , Shigehiro Ono  1 , Kei Tobiume  1 , Kouji Ohta  2 , Masaaki Takechi  1
Affiliations

Effects of miR-224-5p-enhanced downregulation of pannexin-1 on docetaxel-induced apoptosis in amoeboid-like CD44high oral cancer cells

Sho Yokoyama et al. Eur J Oral Sci. 2021 Oct.

Abstract

We previously found that microRNAs play major roles in the maintenance of amoeboid-like oral squamous cell carcinoma (OSCC) cells with high expression of CD44 (CD44high ). However, the roles of microRNAs in chemotherapeutic resistance exhibited by CD44high amoeboid-like OSCC cells are unclear. Here, docetaxel-induced apoptosis was examined in CD44high OSCC cells (CD44high OM-1 cells) cultured on laminin-coated silicone gel. Amoeboid-like CD44high OSCC cells exhibited robust resistance to docetaxel-induced apoptosis and significant upregulation of miR-224-5p expression compared with epithelial-like CD44high OSCC cells and mesenchymal-like CD44high OSCC cells. The expression of pannexin-1 (PANX1), a channel-forming protein that regulates the release of ATP, was significantly upregulated following transfection of amoeboid-like CD44high OSCC cells with an miR-224-5p inhibitor. These results suggest that miR-224-5p inhibits PANX1 expression. Furthermore, miR-224-5p inhibitor-transfected amoeboid-like CD44high OSCC cells exhibited significant enhancement of the proportion of apoptotic cells; however, this effect was significantly inhibited by knockdown of PANX1 with PANX1 small interfering RNA. Additionally, the miR-224-5p inhibitor-enhanced extracellular ATP levels were significantly reduced by PANX1 knockdown. These findings imply that miR-224-5p plays a vital role in the resistance to docetaxel-induced apoptosis by attenuating PANX1-induced ATP discharge. Moreover, amoeboid-like CD44high OSCC cells may be involved in chemotherapeutic resistance of OSCC.

Keywords: cancer stem cell; chemotherapeutic resistance; oral squamous cell carcinoma.

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References

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