MiRNAs are small snippets of genetic information that are thought to be able to regulate up to 60% of the genome. While they were discovered in the 1990s, their use in cancer treatment and diagnostics is still young. Oral squamous cell carcinomas (OSCCs), one of the deadliest head and neck cancers with a poor prognosis and high recurrence. A group from Shanghai hypothesized a miRNA, miR148a, may help diagnose, or even treat, OSCC.
MiR148a is a miRNA that has appeared in several studies linking it to gastric, lung, esophageal, oral cancers. Its overexpression in in vitro experiments was found to inhibit the proliferation of cancer cells. Using this as a base, the team decided to investigate MiR148a in patients with OSCC. They gathered 110 patients with OSCC. Sixty-six patients were in stages one or two, while forty-four were in stages three or four. Using qRT-PCR, the levels of miR148a were measured for each patient. Lower levels of miR148a were found to correlate with OSCCs that had metastasized. Follow up in vitro experiments using cancer cell lines with low miR148a expression found that increasing miR148a levels inhibited the cells’ cellular proliferation and growth.
Setting out to investigate the mechanism by which miR148a worked as a tumor suppressor, they ran a binding sequence screen. They found the insulin-like growth factor receptor 1 (IGF-IR) gene to be a likely candidate for binding. MiR148a could theoretically bind to an untranslated region of the gene and inhibit its expression. IGF-IR is a tyrosine kinase that has been implicated in cancer progression by increasing cellular proliferation, possibly through the activation of the ERK/MAPK pathway, which controls cellular proliferation and division. Indeed, in vitro assays showed that when miR148a was expressed, IGF-IR was down-regulated, which decreased activated proteins of the ERK/MAPK pathway. Taking away miR148a, or overexpressing IGF-IR, reactivated the pathway and led to an increase in cancer cell growth. This effectively connected miR148a to the suppression of the ERK/MAPK pathway, a common pathway upregulated in many cancers.
The group states, “In conclusion, miR-148a expression is down-regulated in OSCC and it may inhibit the progression of OSCC through inactivating ERK/MAPK signaling pathway via targeting IGF-IR.” The toolkit in the fight against cancer is expanding every day. MiRNAs like miR148a are great options for biomarkers that can be used to detect cancer both before and after treatment. There may be a route where they can even be used for treatments. There is still a lot to learn about them; however, further research continues to bring them into clarity.
Sources: Portland Press, Random42 Scientific Communication
