(SST) Brainlab Neurosurgery Award (2023 Award Winner): The Long Noncoding RNA-ASLNC09520 Switches the Role of KLF4 as an Oncogene and Tumor Suppressor During the Malignant Progression of Meningiomas
Chief Neurosurgeon Huashan Hospital, Fudan University Shanghai, China (People's Republic)
Disclosure(s):
Hailiang Tang, MD, PHD: No financial relationships to disclose
Introduction: We previously demonstrated that Krüppel-like factor 4 (KLF4) was a tumor suppressor in malignant meningioma. However, the precise role of KLF4 in the pathogenesis of meningioma remains unclear.
Methods: We analyzed and compared KLF4 expression levels in different grades of meningiomas. Then we conducted deep analysis of the causes for the mutual transition of the two pathways (KLF4/hsa-miR150-5p/P53 and KLF4/P53), and confirmed the theory of the existence of ASLNC09520 (one kind of lncRNAs), which is a key factor in the transition of the two pathways. Based on the mechanism research, we tried to achieve the mutual conversion of KLF4 gene as tumor suppressor or cancer promotion function by intervening ASLNC09520 through gene intervention experiments, and furtherly, we completed the subcutaneous tumor-bearing inhibition experiment in nude mice by ASLNC09520 intervention.
Results: Mechanistic studies shown that in the progression of meningioma, KLF4 changes from having properties of oncogene to having those of tumor-suppressor gene, and this process is facilitated by a switch between the KLF4/hsa-miR150-5p/P53 and KLF4/P53 pathways, with ASLNC09520 playing a key role in this process. High levels of ASLNC09520 in malignant meningiomas competitively bind hsa-miR150-5p in the form of miRNA sponge, which blocks the KLF4/hsa-miR150-5p/P53 pathway and ensures its tumor suppression effects through the KLF4/P53 pathway. Conversely, in benign meningiomas, the ASLNC09520 content is extremely low, and the KLF4/hsa-miR150-5p/P53 pathway is dominant. Functional experiments also confirmed that the overexpression of ASLNC09520 in benign meningiomas can change the oncogene KLF4 into a tumor suppressor. Conversely, knockdown of ASLNC09520 in malignant meningioma cells switches KLF4 from a tumor suppressor back to an oncogene.
Conclusion : Our study is the first report of ASLNC09520 in meningioma progression and is the first to elaborate the role of lncRNA as a key factor in the cancer-promoting and tumor suppressor transformation of KLF4 in different stages of meningioma.
