LncRNA-IMAT1 Promotes Invasion of Meningiomas by Suppressing KLF4/hsa-miR22-3p/Snai1 Pathway

Abstract

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

Noncoding RNA landscape and their emerging roles as biomarkers and therapeutic targets in meningioma

“… 95 However, the mechanism for meningioma invasion is currently not very well known and needs to be studied further. A recent study 96 reported that lncRNA-invasive meningioma-associated transcript 1 ( IMAT1 ) is highly expressed in invasive meningiomas compared with noninvasive meningiomas. IMAT1 binds to and regulates the expression of hsa-miR22-3p.…”

“…It has also been reported that IMAT1, showing higher expression in aggressive meningiomas, can promote meningioma progression, and can be a potential diagnostic, therapeutic, and prognostic molecule. 96 …”

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

“…LncRNAs can bind chromatin, attract protein complexes to modify chromatin states, and subsequently control gene expression [164]. In one instance, lncRNAs can control miRNA function by acting as endogenous miRNA sponges to inhibit miRNA function and consequently block the silencing of miRNA target genes [165]. Differential profiling of patients with different meningioma grades and recurrences revealed that mRNA levels of immunoglobulin superfamily containing leucine-rich repeat 2 (ISLR2), anti-mullerian hormone (AMH), and lncRNA-GOLGA6A-1 exhibited the highest prognos-tic power to predict meningioma recurrence (Table 1) [72].…”

“…Interestingly, ISLR2, AMH, and lncRNA-GOLGA6A-1 transcription is controlled by several transcription factors including KLF4, which is linked to activating mutations of meningiomas [72]. Invasive meningiomaassociated transcript 1 (IMAT1) is an lncRNA, which was shown to be expressed more strongly in invasive than non-invasive meningiomas [165]. IMAT1 overexpression significantly increased proliferation and invasion of human meningioma cells expressing KLF4.…”

Hsa_circ_0004872 alleviates meningioma progression by sponging miR-190a-3p/PTEN signaling

“…Meningioma, constituting 36.6% of all primary central nervous system (CNS) malignancies [ 1 ], poses a significant health challenge. Classified into benign (Grade I), atypical (Grade II), and anaplastic (Grade III) tumors according to the 2021 WHO CNS tumor grading guidelines [ 2 ], malignant meningiomas (Grade II/III) exhibit high recurrence rates and dismal prognoses, profoundly impacting patient survival and quality of life [ 3 ]. Understanding the etiology of malignant meningioma is crucial for devising innovative treatment strategies.…”