FZD6 expression is negatively regulated by miR-199a-5p in human colorectal cancer

Abstract

Colorectal cancer (CRC), the third most common cancer worldwide, also has the highest rate of cancer-related morbidity and mortality. WNT signaling is initiated by binding of WNT to various receptors, including frizzleds (FZDs), and plays a critical role in CRC and other tumor development by regulating proliferation, differentiation, migration, apoptosis, and polarity. Among the members of the FZD family, FZD6 is broadly expressed in various tissues, and its overexpression has been reported in several cancers, suggesting an important role in cancer development. In this study, we investigated the expression of FZD6 in patients with CRC and found it to be increased in tumors, as compared to paired adjacent non-tumor tissues. Additionally, we found that FZD6 expression was negatively regulated by miR199a5p in CRC cells. These results suggest that overexpression of FZD6, mediated by reduced expression of miR-199a-5p, may play an important role in the development of CRC. [BMB Reports 2015; 48(6): 360-366]

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer

“…Many studies have observed through mutagenesis experiments that several residues in the intracellular loops and the C-terminus of FZD play a prominent role in signaling (Cong et al, 2004;Wallingford and Habas, 2005). Kim et al (2015) found that the expression of FZD6 was increased in colorectal cancer (CRC) patients when compared to that in nontumor tissues. Furthermore, they discovered that FZD6 expression in CRC cells was negatively regulated by miR199a-5p (Kim et al, 2015).…”

“…Kim et al (2015) found that the expression of FZD6 was increased in colorectal cancer (CRC) patients when compared to that in nontumor tissues. Furthermore, they discovered that FZD6 expression in CRC cells was negatively regulated by miR199a-5p (Kim et al, 2015). In recent research, Corda et al (2017) observed that the Wnt receptor-encoding gene FZD6 is often duplicated in breast cancer and confers a higher risk of triple-negative breast cancer.…”

Downregulation of miR‐199a/b‐5p is associated with GCNT2 induction upon epithelial–mesenchymal transition in colon cancer

“…These results strongly suggest that downregulation of miR‐199 is at least partly responsible for the observed induction of GCNT2 upon EMT of colon cancer cells. Consistent with these results, the levels of miR‐199 family members are downregulated in metastatic lesions in contrast with the primary tumor as seen in clinical samples of colon cancers, and miR‐199 suppresses colon cancer metastasis in vivo . It has been suggested that the miR‐199 family regulates the progression and metastasis of various cancers other than colon cancer, including liver, ovarian, prostate, and breast cancers .…”

MiR‐199a‐5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma

“…It is well known that miRNAs function via regulating their target protein by binding to the 3’ untranslated regions (UTRs) of target messenger RNAs (mRNAs), resulting in mRNA degradation or the blockade of mRNA translation . Previously, miR‐199a‐5p was reported to functions as a tumor suppressor by targeting connective tissue growth factor (CTGF), integrin β1, hypoxia‐inducible factor 1 alpha (HIF‐1α), E‐cadherin, hexokinase 2, frizzled class receptor 6 (FZD6), E2F transcription factor 3 (E2F3), Wnt family member 2 (WNT2) and cyclin‐dependent kinase inhibitor 1C (P57, CDKN1C) …”

“…In present study, we showed that miR-199a-5p, frequently down- 19,20 Previously, miR-199a-5p was reported to functions as a tumor suppressor by targeting connective tissue growth factor (CTGF), integrin β1, hypoxia-inducible factor 1 alpha (HIF-1α), E-cadherin, hexokinase 2, frizzled class receptor 6 (FZD6), E2F transcription factor 3 (E2F3), Wnt family member 2 (WNT2) and cyclin-dependent kinase inhibitor 1C (P57, CDKN1C). [21][22][23][24][25][26][27][28][29] Clathrin is considered the prototype vesicle coat protein whose self-assembly mediates sorting of membrane cargo and recruitment of lipid modifiers. 30 In the past decades, most of studies were focused on clathrin mediated endocytosis.…”