KLF12

Last update 08 May 2025

Basic Info

Synonyms

AP-2rep, AP2REP, HSPC122

+ [4]

Introduction

Confers strong transcriptional repression to the AP-2-alpha gene. Binds to a regulatory element (A32) in the AP-2-alpha gene promoter.

100 Clinical Results associated with KLF12

100 Translational Medicine associated with KLF12

0 Patents (Medical) associated with KLF12

145

Literatures (Medical) associated with KLF12

01 May 2025·International Journal of Biological Macromolecules

KLF12 transcriptional activation by a novel LncRNA A930015D03Rik enhances melanoma metastasis

Article

Author: Xiang, Meng ; Su, Jie ; Xie, Jiacheng ; Li, Ziyi ; Han, Xue ; Xing, H Rosie ; Zhang, Yuhan ; Li, Jingyu ; Guo, Shimeng ; Dai, Xue ; Tan, Jiyu ; Tang, Yao ; Zhang, Sicheng ; Wang, Jianyu

Melanoma metastasis remains a poorly understood yet fatal hallmark of cancer progression, with limited therapeutic strategies targeting its underlying mechanisms. While the transcription factor KLF12 shows paradoxical roles across malignancies, its context-dependent functions in melanoma-particularly its regulatory interplay with extracellular vesicle (EV)-driven intercellular communication-have not been systematically explored. To address this gap, we investigated how metastatic melanoma cells exploit KLF12-mediated pathways through EV cargo transfer to propagate aggressive phenotypes. Our research results indicate that highly metastatic cells transfer lncRNA A930015D03Rik through exosomes, acting as a sponge for miR-204-5p, which promotes the expression of KLF12. The transcriptional activation of KLF12 facilitates the activation of critical pro-cancer pathways such as inflammation and NF-κB, while inhibiting the tumor-suppressive mechanisms of P53 and oxidative phosphorylation. This ultimately enhances the migration and invasion capabilities of low-metastatic tumor cells, driving the malignant progression of melanoma. In this study, we identified a novel tumor-derived EVs lncRNA, A930015D03Rik, which can enhance the expression of KLF12 through a ceRNA mechanism and influence the post-translational regulation of KLF12, thereby modulating the plasticity of tumor metastasis. This exosome-genome feedforward circuit explains KLF12's microenvironment-contingent pro-metastatic function, offering significant insights for the development of future therapeutic strategies targeting tumor metastasis.

01 Mar 2025·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

KLF12 inhibits lipopolysaccharide-induced inflammatory responses, oxidative stress, pyroptosis, and endoplasmic reticulum stress in human airway epithelial cells through inhibition of the NF-κB pathway

Article

Author: Yu, Yiping ; Xu, Xiujuan

Asthma is a common and frequent chronic disease in pediatrics with obvious pathological features, particularly inflammation, oxidative stress, pyroptosis, and endoplasmic reticulum (ER) stress. Some Krüppel-like factors (KLFs), such as KLF2, KLF4, KLF5, and KLF10, have been reported to be associated with several respiratory diseases, including asthma. However, the role of KLF12 in asthma pathogenesis is unknown. Based on the GEO analysis, KLF12 mRNA expression was reduced in asthma patients. We further assessed the role of KLF12 in protecting airway epithelial cells (BEAS-2B cells) against stimuli using an in vitro model of asthma. The results showed that lipopolysaccharide (LPS) stimulation caused a decrease in KLF12 expression. LPS-induced increase in the mRNA levels of inflammatory cytokines TNF-α, IL-6, and IL-8 were attenuated by KLF12 overexpression. LPS induced the production ROS and MDA and reduced the activities of enzymatic antioxidants SOD, CAT, and GSH-Px, which were prevented by KLF12 overexpression. KLF12 overexpression also blocked LPS-induced pyroptosis, as shown by decreased levels of IL-1β, IL-18, and LDH, as well as downregulated expression levels of pyroptosis-related proteins including NLRP3, ASC, cleaved caspase-1, and GSDMD-N. LPS-induced expression levels of ER stress markers GRP78, CHOP, p-eIF2α, and ATF-4 were inhibited by KLF12 overexpression. In addition, the protective effects of KLF12 on LPS-stimulated cells were enhanced by PDTC, an inhibitor of NF-κB. KLF12 knockdown showed an opposite effect to KLF12 overexpression. These results indicated that KLF12 suppressed LPS-induced inflammatory response, oxidative stress, pyroptosis, and ER stress, which were mediated by the inactivation of the NF-κB pathway.

04 Feb 2025·Journal of the American Heart Association

KLF12 Aggravates Angiotensin II‐Induced Cardiac Remodeling in Male Mice by Transcriptionally Inhibiting SMAD7

Article

Author: Wang, Sha‐Sha ; Hu, Min ; Gao, Yi‐Peng ; Zeng, Xiao‐Feng ; Tang, Qi‐Zhu ; Huang, Shi‐Yu ; Teng, Teng ; Hu, Yu‐Xin

BackgroundAdverse left ventricular remodeling and subsequent heart failure remain a major cause of patient morbidity and mortality worldwide. The KLF family of transcription factors plays crucial roles in heart injury. KLF12 (Krüppel‐like factor 12) is a transcription factor that regulates multiple disease processes, although the specific role of KLF12 in cardiac remodeling remains unclear.Methods and ResultsIn our study, we observed a significant upregulation of KLF12 expression in remodeling hearts. The increased expression of KLF12 primarily originated from cardiac fibroblasts during the fibrotic response induced by angiotensin II. To investigate the effects of KLF12, we performed RNA‐seq and found that KLF12 overexpression significantly upregulated the cardiac remodeling associated pathway. Hence, we generated adult mice with cardiac fibroblast‐specific overexpression of KLF12 using lentivirus or miRNA (miR‐1/133TS) technology. Compared with control mice, KLF12‐miR1/133TS transfected mice exhibited exacerbated cardiac remodeling and function. Mechanistically, we discovered that KLF12 directly binds to the promoter of Smad7, leading to the activation of the TGF‐β (transforming growth factor beta)‐Smad3 pathway.ConclusionsIn conclusion, KLF12 promoted the development of angiotensin II‐induced cardiac remodeling in male mice. Targeting KLF12 may be a promising therapeutic approach to treat cardiac remodeling.

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KLF12

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