Krüppel-like factor 4 contributes to the pathogenesis of mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. Krüppel-like factor 4 (KLF4) has been reported as a bi-regulator in malignancies, but little is known about its role in MCL. Here, we showed that KLF4 was downregulated in three MCL cell lines and lymph nodes from MCL patients, which resulted in a negative prognosis. We also found that the regulation of KLF4 could inhibit the proliferation and induce apoptosis of Jeko-1 cells. The lentivirally over-expressed KLF4 protein was found bind to β-catenin and could inhibit downstream molecules such as cyclinD1 and c-Myc. Furthermore, 5-azacytidine could decrease the expression of methyltransferase-1 (DNMT-1) and restore the KLF4 expression in MCL cell lines, indicating that methylation might play an important role in the downregulation of KLF4. KLF4 may be a potential therapeutic target as a tumor suppressor in MCL.

Keywords:

• Mantle cell lymphoma
• KLF4
• Wnt/β-catenin pathway
• tumor suppressor
• 5-azacytidine

Acknowledgements

This study was partly supported by: National Natural Science Foundation (No. 81473486 and No. 81270598), National Public Health Grand Research Foundation (No. 201202017), Natural Science Foundations of Shandong Province (No. ZR2012HZ003 and No. 2009ZRB14176), Technology Development Projects of Shandong Province (No. 2014GSF118021, No. 2010GSF10250, and No. 2008GG2NS02018), Program of Shandong Medical Leading Talent, and Taishan Scholar Foundation of Shandong Province.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2017.1292354.