Down-regulation of KIAA1199/CEMIP by miR-216a suppresses tumor invasion and metastasis in colorectal cancer

Abstract

Colorectal cancer is one of the major causes of death from cancer. Metastasis is the leading cause of treatment failure, in which cancer stem cells and circulating tumor cells play crucial roles. Identifying the involved metastatic biomarkers and clarifying the regulation mechanisms are of great importance for targeting tumor metastasis. In the current research, we discovered that KIAA1199, a cell-migration inducing protein, showed higher expression in CD44+ cancer cells from metastatic compared with the paired primary tissues, and was upregulated in colorectal cancer and positively correlated with numbers and mesenchymal phenotype of circulating tumor cells, and predicted shorter progress-free survival. Moreover, we indicated that down-regulation of KIAA1199 suppressed migration and invasion of colorectal cancer cells in vitro, and inhibited metastasis in vivo. Furthermore, we demonstrated that KIAA1199 was one of the direct and functional targets of miR-216a, and miR-216a overexpression led to decreased migration and invasion of colorectal cancer cells in vitro, and inhibited metastasis in vivo. Collectively, KIAA1199 plays a critical role in maintaining an aggressive phenotype of tumor cells, and suppression of KIAA1199-related motilities of tumor cells contributes to reduced tumor metastasis in colorectal cancer.

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

“…Specifically, hsa-miR-216a was positively associated with patients' prognosis. The miR-216a has been reported to be a tumor suppressor in pancreatic cancer and colorectal cancer [31,32]，which is in line with our data. We found that miR-301b and miR-96 were significantly upregulated in TNBC compared with control.…”

miR-216a-5p acts as an oncogene in renal cell carcinoma

“…Available research literature suggests that higher or lower expression of miR-216a-5p occurs in a variety of cancers. Some studies have shown that the expression levels of miR-216a-5p is downregulated in colorectal cancer (16) and pancreatic cancer (17), while others have reported upregulated levels of miR-216a-5p in prostate cancer (18) and liver cancer (19). Intracellular environments of different cells were diversiform, so the signaling pathways of miR-216-5p were described in certain types of tumor.…”

“…MiR-216a-5p in colorectal cancer has been shown to be upregulated and is responsible for maintaining the aggressive phenotype of tumor cells (16). Hou et al (22) have demonstrated that miR-216a-5p significantly inhibits cell growth and promotes cell apoptosis by targeting the Janus kinase 2 (JAK2) and transcription 3 (STAT3) in pancreatic cancer (22).…”

“…Previous studies have demonstrated that miR-216a-5p is dysregulated in a number of malignancies, such as colorectal cancer, pancreatic cancer, prostate cancer and liver cancer (16)(17)(18)(19). However, the expression of miR-216a-5p requires quantification and the role of miR-216a-5p in RCC has not been investigated to date.…”

A biosystems approach to identify the molecular signaling mechanisms of TMEM30A during tumor migration

“…Pathology observations in vivo indicate that tumor cells migrate in two main ways: individually and collectively [4, 8], knowledge of which has attracted efforts focusing on cell adhesion, epithelial to mesenchymal transition, angiogenesis, lymphangiogenesis and organ-specific metastasis [7]. Moreover, related molecules including cell adhesion factors [9, 10], growth factors [11], microRNA [3, 12], and lncRNA [13, 14] has been reported to be active during the metastatic cascade. Mounting evidence also indicates that inaddition to internal molecules, external influences modulate tumor migration and invasion [1, 2, 7, 15], such as chemical signals [16] and excessive amounts of exosomes released by tumor cells [17].…”