Effects of miR-224-5p-enhanced downregulation of pannexin-1 on docetaxel-induced apoptosis in amoeboid-like CD44 high oral cancer cells

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 (CD44 ). However, the roles of microRNAs in chemotherapeutic resistance exhibited by CD44 amoeboid-like OSCC cells are unclear. Here, docetax...

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Published in:European journal of oral sciences 2021-10, Vol.129 (5), p.e12812
Main Authors: Yokoyama, Sho, Shigeishi, Hideo, Murodumi, Hiroshi, Sakuma, Miyuki, Ono, Shigehiro, Tobiume, Kei, Ohta, Kouji, Takechi, Masaaki
Format: Article
Language:English
Subjects:
Amoeba
Apoptosis
Carcinoma, Squamous Cell - genetics
Connexins
Docetaxel - pharmacology
Down-Regulation
Humans
Hyaluronan Receptors
MicroRNAs - genetics
Mouth Neoplasms - genetics
Nerve Tissue Proteins
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Summary: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 (CD44 ). However, the roles of microRNAs in chemotherapeutic resistance exhibited by CD44 amoeboid-like OSCC cells are unclear. Here, docetaxel-induced apoptosis was examined in CD44 OSCC cells (CD44 OM-1 cells) cultured on laminin-coated silicone gel. Amoeboid-like CD44 OSCC cells exhibited robust resistance to docetaxel-induced apoptosis and significant upregulation of miR-224-5p expression compared with epithelial-like CD44 OSCC cells and mesenchymal-like CD44 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 CD44 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 CD44 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 CD44 OSCC cells may be involved in chemotherapeutic resistance of OSCC.
ISSN:0909-8836
1600-0722
DOI:10.1111/eos.12812