MicroRNA 32 promotes cell proliferation, migration, and suppresses apoptosis in colon cancer cells by targeting OTU domain containing 3

Abstract

Colorectal cancer is considered as the fourth leading reason of cancer‐linked deaths worldwide. However, our knowledge about its pathogenic mechanism remains inadequate. MicroRNA 32 (miR‐32), a member of small noncoding RNAs, has been found vital roles in tumorigenesis. This study studied its functions and underlying mechanism in colorectal cancer. The experiment revealed the obvious upregulation of miR‐32 in colorectal cancer tissues and six cancer cell lines, compared with normal tissues and cells. Moreover, miR‐32 upregulation reduced cell apoptosis and promoted cell proliferation and migration, while its downregulation displayed opposite effects. Dual luciferase reporter assays proved that miR‐32 bound to the 3′‐untranslated region (3′‐UTR) of OTU domain containing 3 (OTUD3), suggesting that miR‐32 directly targeted OTUD3. Further experiments demonstrated that overexpression of miR‐32 could reduce the expression level of OTUD3. Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR‐32‐mediated cell proliferation, migration, and antiapoptosis for colon cancer. Therefore, our study indicated that miR‐32 enhanced cell proliferation and motility abilities, and inhibited apoptosis by directly targeting OTUD3 in colon cancer cells, which implied that miR‐32 was hopeful to be a biomarker or target used for diagnosis and therapy of colon cancer.

Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis

“…For example, relevant studies found that miR-181a can promote angiogenesis in CRC tissues by regulating SRCIN1 so that SRC/VEGF signaling pathway can be promoted [ 12 ]. Jin Y et al observed that miR-32 plays a key role in cell proliferation and migration, as well as in suppressing apoptosis in colon cancer [ 13 ]. These studies further enhance the essential roles of microRNAs in cancer and the necessity of identifying novel CRC biomarkers.…”

MicroRNAs and Apoptosis in Colorectal Cancer

“…The miR-32 inhibited apoptosis by directly targeting OTUD3 in colon cancer cells. The miR-32 upregulation reduced cell apoptosis, while its downregulation displayed opposite effects [ 103 ]. The decrease in FAS expression could contribute to the reduction of apoptosis in CRC cells.…”

The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases

“…Recent studies showed that OTU deubiquitinases can act as either positive or negative regulators in different types of cancer. For instance, OTU deubiquitinase 3 (OTUD3) expression level decreases directly via microRNA-32 targeting, which leads to enhanced proliferation in the HCT116 colorectal cell line [89]. On the other hand, the overexpression of ubiquitin aldehyde binding 1 (OTUB1) was detected in colorectal cancer tissues, which induced the metastasis both in vivo and in vitro studies via triggering the epithelial-mesenchymal transition [90].…”