MicroRNAs Are Involved in Regulating Colorectal Cancer Metastasis via the CD44 Receptor

Knockdown of CD44 in colorectal cancer tumours alters the expression of microRNAs and their targets involved in epithelial–mesenchymal transition and the Notch signalling pathway, both of which are associated with tumour metastasis

© D. V. Maltseva.​

The formation of metastases remains a serious challenge in oncology, as it greatly reduces survival in patients with colorectal cancer. Recent studies by the International Laboratory of Microphysiological Systems at HSE University, conducted in collaboration with international colleagues, have shown that suppression of CD44 receptor activity reduces hypoxia and epithelial–mesenchymal transition (EMT) in colorectal cancer xenograft tumours, collectively decreasing their metastatic potential in experimental animals. ​

In this work, the researchers sought to gain deeper insight into the molecular mechanisms underlying the changes observed in tumours after CD44 knockdown. The results revealed seven canonical microRNAs (let‑7a‑5p, let‑7b‑5p, let‑7c‑5p, miR‑203a‑3p, miR‑101‑3p, miR‑185‑5p and miR‑125a‑5p) and two 5′‑isomiRs (miR‑203a‑3p|+1 and miR‑200b‑3p|+1). Bioinformatic analysis showed that these microRNAs and their gene targets are involved in key processes linked to metastasis, including EMT and the Notch signalling pathway, suggesting that they may contribute to the reduced metastatic activity of tumours observed after CD44 knockdown. The results have been published in Frontiers in Immunology.