MicroRNA-200c Modulates the Expression of MUC4 and MUC16 by Directly Targeting Their Coding Sequences in Human Pancreatic Cancer

Abstract

Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression and metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts with specific sequences within the coding sequence of MUC4 and MUC16 mRNAs, and evaluated the regulatory nature of this association. Pancreatic cancer cell lines S2.028 and T3M-4 transfected with miR-200c showed a 4.18 and 8.50 fold down regulation of MUC4 mRNA, and 4.68 and 4.82 fold down regulation of MUC16 mRNA compared to mock-transfected cells, respectively. A significant reduction of glycoprotein expression was also observed. These results indicate that miR-200c overexpression regulates MUC4 and MUC16 mucins in pancreatic cancer cells by directly targeting the mRNA coding sequence of each, resulting in reduced levels of MUC4 and MUC16 mRNA and protein. These data suggest that, in addition to regulating proteins that modulate EMT, miR-200c influences expression of cell surface mucins in pancreatic cancer.

MiR-211 inhibits invasion and epithelial-to-mesenchymal transition (EMT) of cervical cancer cells via targeting MUC4

“…Several miRNAs have suppressive effect on MUC4 expression, such as miR-200c, miR-150 and miR-219-1-3p [11][12][13]. By performing bioinformatics analysis, we also observed that miR-211 is a potential suppressor of MUC4, which has a predicted highly conserved binding site in the 3'UTR of MUC4 among mammals.…”

“…Actually, the involvement of MUC4 in EMT of some cancer cells were also observed. MUC4 dependent upregulation of N-cadherin and associated EMT was observed in pancreatic, ovarian and breast cancer cells [7,9,12]. Mechanistically, MUC4 can interact with HER2 and subsequently activate FAK/MKK7/JNK and c-Jun to regulate the N-cadherin expression [5].…”

“…Multiple studies demonstrated that some miRNAs have suppressive effect on MUC4 expression. For example, miR-200c, miR-150 and miR-219-1-3p can decrease MUC4 expression in pancreatic cancer and act as tumor suppressor [11][12][13].…”

MiR-103a-3p targets the 5′ UTR of GPRC5A in pancreatic cells

“…Nonetheless, the field has made great advances during this time and numerous miRNA targets have been described in the literature to date with the majority of these targets being located in the 3 ′ UTR of the targeted mRNAs (Bartel 2009). In recent years, others and we have shown that miRNAs can also target mRNAs within their CDS and decrease the corresponding protein's abundance (Duursma et al 2008;Forman et al 2008;Lal et al 2008;Shen et al 2008;Tay et al 2008;Rigoutsos 2009;Brest et al 2011;Hao et al 2011;Nelson et al 2011;Sauna and Kimchi-Sarfaty 2011;Gartner et al 2013;Hausser et al 2013;Radhakrishnan et al 2013;Shabalina et al 2013).…”

The microRNA-218 and ROBO-1 signaling axis correlates with the lymphatic metastasis of pancreatic cancer

“…miRNAs also play a role in the progression of tumor and are termed as oncomiR or anti-oncomiR. In pancreatic cancer, investigators have found some miRNAs, including miR-96, miR-217, let-7 and miR-34 (2)(3)(4)(5), that serve as tumor suppressors, and another class of miRNAs, including miR-21, miR-155 and miR-200 family members (6)(7)(8)(9), that promote tumor progression.…”