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| Content Provider | Springer Nature Link |
|---|---|
| Author | Maqbool, Raihana Rashid, Rabiya Ismail, Rehana Niaz, Saif Chowdri, Nisar Ahmad Hussain, Mahboob Ul |
| Copyright Year | 2015 |
| Abstract | Connexin 43 (Cx43) is a widely expressed gap junction protein. It can also regulate various gap-junction independent processes, including cellular proliferation. The latter regulatory functions have been attributed to its carboxy-terminal domain, CT-Cx43. CT-Cx43 has been found to be expressed independent of full-length Cx43 in various cell types. Its nuclear localization has additionally raised the possibility that it may regulate the expression of particular genes, including miRNAs, known play a role in the regulation of cellular proliferation. Here, we set out to uncover the molecular mechanism(s) underlying CT-Cx43 mediated gene (de-)regulation in human breast cancer.Western blotting and quantitative real time PCR were carried to assess the expression of CT-Cx43 and miR-125b in a panel of 60 primary human breast cancer tissues and its paired normal adjacent tissues. In addition, CT-Cx43 was exogenously expressed in the breast cancer-derived cell line MCF-7 and its effect on the expression of miR-125b and its downstream target p53 were evaluated, as well as its effect on cellular proliferation and death using MTT and LDH assays, respectively.We found that CT-Cx43, but not full-length Cx43, was down-regulated in low grade human breast cancers. In addition, we found that the tumor suppressor protein p53 exhibited a decreased expression in the CT-Cx43 down-regulated samples. Interestingly, we found that miR-125b, a negative regulator of p53, exhibited an inverse expression relationship with CT-Cx43 in the breast cancer samples tested. This inverse relationship was confirmed by exogenous expression of CT-Cx43 in MCF-7 cells. In addition, we found that CT-Cx43 up-regulation and subsequent miR-125b down-regulation resulted in a decreased proliferation of MCF-7 cells.Our data suggest a mechanism by which CT-Cx43 may regulate cell proliferation. Targeting of CT-Cx43 and/or miR-125b may be instrumental for therapeutic intervention in human breast cancer. |
| Starting Page | 443 |
| Ending Page | 451 |
| Page Count | 9 |
| File Format | |
| ISSN | 22113428 |
| Journal | Cellular Oncology |
| Volume Number | 38 |
| Issue Number | 6 |
| e-ISSN | 22113436 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2015-09-03 |
| Publisher Institution | International Society for Cellular Oncology |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Connexin43 miR-125b p53 Breast cancer Cancer Research Biomedicine general Pathology Oncology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Molecular Medicine Oncology |
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