miR‑200b‑3p inhibits proliferation and induces apoptosis in colorectal cancer by targeting Wnt1

Abstract

MicroRNA (miR)-200b-3p is downregulated in multiple human cancer types. Wnt signaling serves a role in human colorectal cancer (CRC). The present study aimed to examine the effect of miR-200b-3p on human CRC and its potential association with Wnt signaling. The Cell Counting Kit-8 (CCK-8) was employed to assess cell viability. A flow cytometric assay was conducted to examine cell proliferation and apoptosis. The regulation model of miR-200b-3p and Wnt1 was assessed by a luciferase reporter assay. A commercial kit was used to evaluate the activity of caspase-3 following treatment of the cells by miR-200b-3p or Wnt1. The expression of target factors was determined by a quantitative real-time polymerase chain reaction and western blot analysis. The expression of miR-200b-3p was decreased in human CRC tissues and in cell lines. The bioinformatics analysis and the luciferase reporter assay revealed that Wnt1 may be a direct target of miR-200b-3p. Moreover, the viability and proliferation of CRC cells was suppressed by miR-200b-3p. miR-200b-3p additionally induced apoptosis in CRC cells. Furthermore, the caspase-3 activity was enhanced in the miR-200b-3p mimics group. The expression of antigen Ki-67 (additionally termed KI-67) and β-catenin was decreased, while the expression of cleaved caspase-3 was increased by miR-200b-3p. In conclusion, miR-200b-3p inhibited proliferation and induced apoptosis in CRC cells by inactivating Wnt/β-catenin signaling. The present study provided potential biomarkers and candidate modalities for the management of CRC.

Long non‑coding RNA PVT1 promotes glioma cell proliferation and invasion by targeting miR‑200a

“…The discovery of the function of lncRNA-PVT1 was also demonstrated by inhibiting the expression of lncRNA-PVT1 in glioma cells. In recent years, a number of studies have confirmed miR-200 family expression disorders in a variety of tumor tissues, wherein they participate in tumor cell proliferation, migration, and invasion and the regulation of biological processes (8)(9)(10)29). Although miR-200a has been demonstrated to target many protein-coding genes, the present study suggested that miR-200a also targets lncRNA-PVT1.…”

“…However, the high expression of lncRNA-PVT1 in tumor cells remains unclear. In recent years, numerous studies have confirmed that miR-200 family expression disorders exist in multiple tumor tissues and participate in the regulation of biological characteristics such as tumor cell proliferation, migration and invasion (8)(9)(10). The miR-200 family inhibits epithelial-mesenchymal transition (EMT) by directly targeting the expression of zinc finger E-box binding homeobox 1/2 (ZEB1/ZEB2) and then inhibits the migration and invasion of tumor cells (11,12).…”

The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors

“…MiR-200b-3p belongs to a miR-200 miRNA family, known to be associated with a wide range of human cancers [ 29 ], and has been mainly reported as a tumor suppressor inhibiting cell growth and motility of breast cancer cells [ 30 ], suppressing metastasis in renal cell carcinoma and breast cancer [ 31 , 32 ], inhibiting proliferation, cell cycle and inducing apoptosis in gastric and colorectal cancers [ 33 , 34 ]. Nevertheless, the role of miR-200b-3p in cancer remains controversial, since studies showing the opposite effects on cancer cells exist [ 35 , 36 ].…”

Emerging Roles of Wnt Ligands in Human Colorectal Cancer

“…Blockade of Wnt1 by WIF-1 or its antibody induced a significant apoptosis of human CRC cells containing mutations of APC, CTNNB1, and AXIN2 (79). Moreover, the ectopic expression of microRNA (miR)-200b-3p and miR-185 could significantly inhibit the proliferation and induce the apoptosis of CRC cells by targeting the canonical Wnt1/β-catenin signaling (80,81). However, researches on the Wnt1 expression in human CRC tissues have yielded some conflicting results that the decrease or the increase of Wnt1 expression was detected in CRC tissues compared with normal colorectal mucosa (25,27), and a study even found that the expression level of Wnt1 was decreased in human CRC tissues and CRC mice, whereas Wnt1 knockdown could still dramatically decrease the cell migration and the invasion of human CRC cells, and β-catenin expression was also enhanced in the tumors, indicating that Wnt1 expression could be regulated by more complicated mechanisms during CRC tumorigenesis (82).…”