Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
These authors contributed equally to this work.
Mol Cells. 2022 Jun 30;45(6):388-402. doi: 10.14348/molcells.2022.2232.
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 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. 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. 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.
恶性脑膜瘤常表现为侵袭性生长，使肿瘤完全切除具有挑战性，且在根治性切除后更易复发。侵袭性脑膜瘤相关转录本 1（IMAT1）是一种长链非编码 RNA，位于染色体 17 上，是我们团队根据侵袭性和非侵袭性脑膜瘤的绝对表达差异鉴定出来的。我们的研究表明，与非侵袭性脑膜瘤相比，IMAT1 在侵袭性脑膜瘤中高表达。研究表明，IMAT1 通过作为 hsa-miR22-3p 的海绵体来失活 Krüppel 样因子 4（KLF4）/hsa-miR22-3p/Snai1 通路，从而促进脑膜瘤细胞侵袭，而 IMAT1 敲低通过保留其肿瘤抑制途径，有效地恢复了 KLF4 的肿瘤抑制特性。进一步的实验证实，IMAT1 沉默可显著抑制皮下肿瘤的生长，并延长荷瘤小鼠的生存期。我们的研究结果表明，IMAT1 的高表达是脑膜瘤进展过程中 KLF4 肿瘤抑制特性丧失的内在原因。因此，我们认为 IMAT1 可能是脑膜瘤的潜在生物标志物和治疗靶点。
