S100A7 Regulates miR‐21 and miR‐29b in Oral Squamous Cell Carcinoma
Authors: Ly Ngoc Han T , Pizarro Jeffrey Kyle , Wang Steven J. , Mercado‐Pimentel Melania Ester 
Published: June 2021

Oral Squamous Cell Carcinoma (OSCC) is a subtype of the head and neck cancers. The survival rate of OSCC patients are 5 years, and 50% of all head and neck squamous cell carcinoma (HNSCC) patients have advanced disease at the time of diagnosis, reflecting the lack of biomarkers for early detection. Immunohistochemical studies in HNSCC patients indicate that S100A7 nuclear expression is associated with poor prognosis, and abundant data have shown that the short RNA sequences of about 22 base pairs, known as microRNA (miRNA)s, regulate several cell processes in cancer. S100A7, as well as, the oncomir (oncogene) miR‐21 plays a role in tumor growth, cancer progression and metastasis; and studies in breast tumor cells have shown that S100A7 increases AKT activation. The survival AKT signaling pathway is known to play a role in cell survival, cell proliferation, and epithelial‐mesenchymal transition (EMT) in cancer. Breast cancer studies have shown that the tumor suppressor miR‐29b is up‐regulated or repressed by S100A7 depending on the presence of the estrogen receptor. In addition, acute myeloid leukemia studies have shown that the mature miR‐29b is encoded by two genes, miR‐29b1 and miR‐29b2, localed in two different chromosomes. Since high levels of S100A7 expression have been associated with poor prognosis in HNSCC patients, we wanted to determine if S100A7 regulates miR‐29b and whether it regulates miR‐21 in OSCC. To investigate further on the molecular mechanism of S100A7 regulation in OSCC, the AKT pathway was inhibited with the ILK/AKT inhibitor, OSU‐T315, to determine its effect in miR‐21 and miR‐29b regulation. We knocked down S100A7 in oral cancer cells, SCC‐9, with GFP‐siRNA/S100A7 constructs and used quantitative real time‐PCR to determine its effect in miR‐21 and miR‐29 expression levels. Also, qRT‐PCR was used to determine if miR‐21 and miR‐29b are regulated by the AKT signaling in SCC‐9 cells treated with OSU‐T315 (IC50 1.2 mM). Additionally, we used MTT assays to determine if S100A7 regulates cell proliferation in SCC‐9 cells. Our data show that knocking down S100A7 significantly down regulates miR‐21 and miR‐29b1, while upregulating miR‐29b2, While inhibition of the AKT signaling with OSU‐T315 has significant similar effects in miR‐21, miR‐29b1 and miR‐29b2 as knocking down S100A7 in SCC‐9 cells. MTT assays with selected SCC‐9/siRNA‐S100A7 cells show significant decrease in cell proliferation (p<0.0003) compared to control cells. These data show that S100A7 and the AKT signaling regulates miR‐21 and miR‐29b, and suggest that the AKT signaling plays a role in the molecular mechanism of action of S100A7 in oral squamous cell carcinoma. Moreover, these data suggest that miR‐29b1 is upregulated, while miR‐29b2 is repressed in oral squamous cell carcinoma.

Support or Funding Information

Department of Otolaryngology‐Head & Neck Surgery College of Medicine University of Arizona, National Cancer Institute Grant P30C8023074

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.