Shear stress and microRNAs for better metastatic cancer management

Abstract

AbstractMetastasis is the process by which cancer cells move from the primary location to establish themselves in a new location in the human body. It is still a significant challenge in cancer management because it is responsible for 90% of cancer‐related deaths. In this work, we present an idea to use shear stress encountered by all metastasizing cells as an elegant means to deactivate metastasizing cancer cells. Shear‐induced ROS and cross‐talk between ROS and miRNA play crucial roles in deactivating metastasizing cancer cells. In addition, there exists a vast therapeutic potential for miRNAs. Therefore, this study explores the effect of shear on miRNAs and reactive oxygen species (ROS), the two molecular mediators in the proposed {shear‐stress}–{miRNA}–{metastasizing‐cancer‐cell‐deactivation} approach. In this context, to understand the effect of defined shear on HCT116 colon cancer cells, they were cultivated in a defined shear environment provided by an appropriately designed and fabricated cone‐and‐plate device. Shear rate affected the culture growth characteristics and the specific intracellular reactive oxygen species level (si‐ROS). HCT116 cell growth was observed at 0 and 0.63 s−1 but not at 1.57 s−1 or beyond. Shear rate induced upregulation of the hsa‐miR‐335‐5p but induced downregulation of hsa‐miR‐34a‐5p. Furthermore, the specific levels of hsa‐miR‐335‐5p, hsa‐miR‐26b‐5p, and hsa‐miR‐34a‐5p negatively correlated with specific intracellular (si)‐hydroxyl radical levels. In addition, some messenger RNAs (mRNAs) in HCT116 cells showed a differential expression under shear stress, notably the ROS‐associated mRNA of PMAIP1. The above miRNAs (and possibly some mRNAs) could be targeted to manage colon cancer metastasis.