General Information of the Disease (ID: M6ADIS0166)
Name
Injuries of spine or trunk
ICD
ICD-11: ND51
Full List of Target Gene(s) of This m6A-centered Disease Response
Dexamethasone-induced Ras-related protein 1 (RASD1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary Mettl14-mediated m6A modification inhibited Dexamethasone-induced Ras-related protein 1 (RASD1) and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature miR-375.
Responsed Disease Injuries of spine or trunk [ICD-11: ND51]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
In-vitro Model C8-D1A Normal Mus musculus CVCL_6379
C8-B4 Normal Mus musculus CVCL_6378
In-vivo Model An incision was made in the skin along the medial dorsal line to the aponeurotic and muscular planes, and the posterior vertebral arches were exposed from T8 to T12. Under the dissection stereomicroscope, 3-mm-long laminectomy was performed on the caudal end of T10 vertebra and the rostral end of T11 vertebra. The Infinite Horizons impactor (Infinite Horizons, L.L.C., Lexington, KY, USA) was adopted to produce the contusion SCI using a force of 60 kdyn/cm2. The SCI model rats were established and randomly assigned to SCI model group, ant-NC (negative control, SCI rats treated with lentiviral (lv)-shRNA NC of Mettl14) group and ant-Mettl14 group (SCI rats treated with lv-shRNA of Mettl14). Rats were subjected to laminectomy and then treated with lv-shRNA Mettl14/lv-shRNA-NC (50 ul/day, 100 nmoL/mL; RiboBio, Guangzhou, China) via an intrathecal injection through lumbar puncture for 3 days (0, 1, and 2 days) after 15 min of SCI modelling. In addition, the unmodeled rats were set as sham group.
Elongation factor 1-alpha 2 (EEF1A2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary Silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated spinal cord injury by inhibiting m6A modification of Elongation factor 1-alpha 2 (EEF1A2) and activating the Akt/mTOR pathway.
Responsed Disease Injuries of spine or trunk [ICD-11: ND51]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
mTOR signaling pathway hsa04150
Cell Process Cell apoptosis
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Specifically, rats were anesthetized with an intraperitoneal injection of 4% pentobarbital sodium (35 mg/kg) after weight measurement. To expose the posterior vertebral arch from T8 to T12, an incision was subsequently made on the skin along the dorsomedial line to the aponeurosis and muscle plane. Laminectomy (3 mm) was performed from the caudal end of the T10 vertebra to the caudal end of the T11 vertebra under a dissection stereomicroscope. Infinite Horizons impactor (Infinite Horizons, L.L.C., Lexington, KY, USA) was utilized to induce contusion SCI at the force of 60 kdyn/cm . The incision was sutured, followed by intramuscular injection of 20000 units of penicillin once a day for three days. Incisions of rats in the sham group (N = 10) were sutured after skin incision without modeling surgery and related treatment. SCI rat model was established and SCI rats were assigned to the following groups (N = 10 per group): SCI group (SCI treatment), SCI + sh-NC group (injected with silencing negative control lentivirus after SCI treatment), SCI + sh-METTL14 + sh-EEF1A2 group (injected with silencing EEF1A2 and silencing METTL14 lentivirus after SCI treatment), SCI + oe-NC group (injected with overexpressed EEF1A2 NC lentivirus after SCI treatment), SCI + oe-EEF1A2 group (injected with overexpressed EEF1A2 lentivirus after SCI treatment), SCI + oe-EEF1A2 + H2O group [injected with overexpressed EEF1A2 lentivirus and treated with 50 mg/kg (i.p.) H2O after SCI treatment] and SCI + oe-EEF1A2 + Perifosine group [injected with overexpressed EEF1A2 lentivirus and treated with 50 mg/kg (i.p.) Perifosine after SCI treatment . Lentivirus treatment was conducted three days following laminectomy (on day 0, 1, and 2). sh-NC, sh-METTL14, sh-EEF1A2, oe-NC, and oe-EEF1A2 lentivirus (50 uL/day, 100 nmoL/mL; RiboBio, Guangzhou, China) were intrathecally injected through lumbar puncture for 15 min per day.
microRNA 375 (MIR375)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary Mettl14-mediated m6A modification inhibited RASD1 and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature microRNA 375 (MIR375).
Responsed Disease Injuries of spine or trunk [ICD-11: ND51]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response mTOR signaling pathway hsa04150
In-vitro Model C8-D1A Normal Mus musculus CVCL_6379
C8-B4 Normal Mus musculus CVCL_6378
In-vivo Model An incision was made in the skin along the medial dorsal line to the aponeurotic and muscular planes, and the posterior vertebral arches were exposed from T8 to T12. Under the dissection stereomicroscope, 3-mm-long laminectomy was performed on the caudal end of T10 vertebra and the rostral end of T11 vertebra. The Infinite Horizons impactor (Infinite Horizons, L.L.C., Lexington, KY, USA) was adopted to produce the contusion SCI using a force of 60 kdyn/cm2. The SCI model rats were established and randomly assigned to SCI model group, ant-NC (negative control, SCI rats treated with lentiviral (lv)-shRNA NC of Mettl14) group and ant-Mettl14 group (SCI rats treated with lv-shRNA of Mettl14). Rats were subjected to laminectomy and then treated with lv-shRNA Mettl14/lv-shRNA-NC (50 ul/day, 100 nmoL/mL; RiboBio, Guangzhou, China) via an intrathecal injection through lumbar puncture for 3 days (0, 1, and 2 days) after 15 min of SCI modelling. In addition, the unmodeled rats were set as sham group.
References
Ref 1 Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri-mir-375 to miR-375. Cell Biosci. 2021 Mar 11;11(1):52. doi: 10.1186/s13578-020-00526-9.
Ref 2 METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury. Cell Death Discov. 2022 Jan 10;8(1):15. doi: 10.1038/s41420-021-00808-2.