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Updated: Feb 13, 2026
MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
Imbalance of a KLF4-miR-7 auto-regulatory feedback loop promotes prostate cancer cell growth by impairing microRNA
Lian-Zi Wei1, Yan-Qing Wang2, Yun-Li Chang1
1State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai, China.
Abstract:
The microRNA-transcription factor auto-regulatory feedback loop is a pivotal mechanism for homeostatic regulation of gene expression, and dysregulation of the feedback loop is tightly associated with tumorigenesis and progression. However, the mechanism underlying such dysregulation is still not well-understood. Here we reported that Krüppel-like factor 4 (KLF4), a stemness-associated transcription factor, promotes the transcription of miR-7 to repress its own translation so that a KLF4-miR-7 auto-regulatory feedback loop is established for mutual regulation of their expression. Interestingly, this feedback loop is unbalanced in prostate cancer (PCa) cell lines and patient samples due to an impaired miR-7-processing, leading to decreased mature miR-7 production and attenuated inhibition of KLF4 translation. Mechanistically, enhanced oncogenic Yes associated protein (YAP) nuclear translocation mediates sequestration of p72, a co-factor of the Drosha/DGCR8 complex for pri-miR-7s processing, leading to attenuation of microprocessors' efficiency. Knockdown of YAP or transfection with a mature miR-7 mimic can significantly recover miR-7 expression to restore this feedback loop, and in turn to inhibit cancer cell growth by repressing KLF4 expression in vitro. Thus, our findings indicate that targeting the KLF4-miR-7 feedback loop might be a potential strategy for PCa therapy.
Insights
Krüppel-like factor 4 (KLF4) and miR-7 form a feedback loop crucial for gene regulation. In prostate cancer, this loop is disrupted, leading to uncontrolled KLF4 expression and tumor growth.
Area of Science:
- Molecular Biology
- Cancer Biology
- Gene Regulation
Background:
- MicroRNA-transcription factor feedback loops are vital for maintaining cellular homeostasis.
- Dysregulation of these loops is linked to cancer development and progression.
- The specific mechanisms behind feedback loop dysregulation in cancer remain unclear.
Purpose of the Study:
- To investigate the role of the Krüppel-like factor 4 (KLF4)-microRNA-7 (miR-7) feedback loop in prostate cancer.
- To elucidate the molecular mechanisms underlying the disruption of this feedback loop in prostate cancer.
Main Methods:
- Investigated the KLF4-miR-7 auto-regulatory feedback loop in prostate cancer cell lines and patient samples.
- Utilized molecular biology techniques to study gene and protein expression, including KLF4, miR-7, and Yes associated protein (YAP).
- Examined the impact of modulating YAP and miR-7 levels on feedback loop restoration and cancer cell growth.
Main Results:
- Identified a KLF4-miR-7 auto-regulatory feedback loop where KLF4 promotes miR-7 transcription, and miR-7 represses KLF4 translation.
- Found this feedback loop to be unbalanced in prostate cancer due to impaired miR-7 processing, caused by YAP-mediated sequestration of p72, a cofactor for Drosha/DGCR8.
- Demonstrated that inhibiting YAP or restoring mature miR-7 expression can re-establish the feedback loop, suppress KLF4, and inhibit prostate cancer cell growth *in vitro*.
Conclusions:
- The KLF4-miR-7 feedback loop is disrupted in prostate cancer by YAP hyperactivity, leading to reduced mature miR-7 and increased KLF4.
- Restoring the integrity of the KLF4-miR-7 feedback loop shows therapeutic potential for prostate cancer.
- Targeting this feedback loop presents a promising strategy for prostate cancer treatment.
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