m6A-centered Disease Response Information
General Information of the Disease (ID: M6ADIS0166)
Name |
Injuries of spine or trunk
|
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ICD |
ICD-11: ND51
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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