Metastasis is the leading cause of cancer-related mortality among patients with cancer. Cancer metastasis begins with detachment of metastatic cells from the primary tumor followed by the travel of the cells to different sites through the circulatory/lymphatic systems and finally settlement and growth of the cells at a distal site [
44]. During the process, metastatic cells undergo detachment, migration, invasion and adhesion. These four essential metastatic steps are interrelated and affected by multiple biochemical events and parameters [
45]. EMT has been shown to play pivotal roles in these steps to promote metastasis. Transforming growth factor-β, (TGF-β), a key driver of EMT, plays an important role in cancer metastasis [
46]. In TGF-β-activated cells, SMAD2 and SMAD3 form complexes with SMAD4 and then translocate into the nucleus to regulate the expression of target genes [
47]. Our previous study indicated that SMAD2 is a target of miR-190-5p and that miR-190-5p suppresses breast cancer metastasis by regulating TGF-β-induced EMT [
12]. Consistent with this, other studies also indicated that miR-190-5p suppresses cell migration, invasion and an EMT-like phenotype by targeting STC2 or PAR1 in breast cancer [
13,
25]. Moreover, miR-190-5p inhibits TGF-β signaling in the lung adenocarcinoma cell line A549 [
48]. Vascular endothelial growth factor is a major contributor to angiogenesis, a vital process in tumor metastasis. miR-190-5p significantly suppresses tumor metastasis and angiogenesis by governing a large group of angiogenic effectors, including TCF4, SMAD2, SMAD4, RAS2, JAK2, IGF1, and HGF [
27]. Consistent with our observation in breast cancer, miR-190-5p overexpression inhibits cell migration and invasion and reverses TGF-β-induced EMT in the HCC cell lines HepG2 and Huh7 by targeting the long noncoding RNA treRNA [
19]. However, the contrary point of view has been reported by other scholars, whose result showed a promoting metastasis function of miR-190 in HepG2 cell lines [
30]. Since the lack of some relevant research works, the issue remains controversial, which needs further researches. Despite this, it’s still undeniable that miR-190-5p functions as a promising antitumor target for clinical applications.
Clusterin, a small heat-shock-like protein, is overexpressed in many solid tumors and regulates the PI3K/AKT pathway. Clusterin was shown to dramatically enhance the migratory and invasive behavior of the normal prostate epithelial cell line PNT1A and the prostate cancer cell line PC3 by regulating the miR-190-5p-PHLPP1 axis, suggesting that miR-190-5p functions as an oncogene in prostate cancer [
29]. Furthermore, miR-190-5p promotes cell migration and invasion by targeting FOXP2 in gastric cancer [
18], suggesting a differential function of miR-190-5p possibly related to the specific disease context.