title: 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.
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Geng
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Xiang-Xiang
authors.initials: XX
authors.lastname: Zhou
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Xiao-Sheng
authors.initials: XS
authors.lastname: Fang
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Hematology , Shandong Provincial Hospital affiliated to Shandong University , Jinan , P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D020522:Lymphoma, Mantle-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051176:beta Catenin
keywords: 5-azacytidine; KLF4; Mantle cell lymphoma; Wnt/β-catenin pathway; tumor suppressor