MicroRNAs: Multifaceted Regulators of Colorectal Cancer Metastasis and Clinical Applications.

Colorectal cancer (CRC) is the third-commonest malignant cancer, and its metastasis is the major reason for cancer-related death. The process of metastasis is highly coordinated and involves a complex cascade of multiple steps. In recent years, miRNAs, as highly conserved, endogenous, noncoding, single-stranded RNA, has been confirmed to be involved in the development of various cancers. Considering that miRNA is also involved in a series of biological behaviors, regulating CRC occurrence and development, we review and summarize the role of miRNAs and related signaling pathways in several CRC-metastasis stages, including invasion and migration, mobility, metabolism, epithelial-mesenchymal transition, tumor-microenvironment communication, angiogenesis, anoikis, premetastatic-niche formation, and cancer stemness. In addition, we review the application of miRNAs as diagnostic CRC markers and in clinical treatment resistance. This review can contribute to understanding of the mechanism of miRNAs in CRC progression and provide a theoretical basis for clinical CRC treatment.

Umbilical Cord Blood-Derived Natural Killer Cells Combined with Bevacizumab for Colorectal Cancer Treatment.

Colorectal cancer (CRC) is among the cancers with the highest incidence globally, and it currently ranks as the fourth leading cause of cancer-related deaths worldwide. Novel strategies for the treatment of advanced CRC are urgently needed, and adoptive transfer of allogeneic natural killer (NK) cells represents an attractive option. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound interleukin (IL)-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of interferon-γ, tumor necrosis factor-α, granulocyte-macrophage colony stimulating factor, and chemokine ligand 3 compared with IL-2-stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. Higher numbers of NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Bevacizumab increased extravasation of adoptively transferred NK cells into LoVo tumors and improved the therapeutic activity of eUCB-NK cells. These results justify clinical translation of UCB-derived NK cell-based therapeutics, used alone or in combination with bevacizumab, as a novel treatment option for patients with CRC.