PMID- 35413492
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20220613
IS  - 1532-3072 (Electronic)
IS  - 0040-8166 (Linking)
VI  - 76
DP  - 2022 Jun
TI  - Analysis of the function and mechanism of DIRAS1 in osteosarcoma.
PG  - 101794
LID - S0040-8166(22)00066-0 [pii]
LID - 10.1016/j.tice.2022.101794 [doi]
AB  - BACKGROUND: Osteosarcoma is a prevalent malignant bone tumor with a tendency to 
      metastasize to the lungs. In this study, we intend to detect the function and 
      mechanism of DIRAS family GTPase 1 (DIRAS1) in osteosarcoma cells. METHODS: 
      Expression level of DIRAS1 in osteosarcoma cells was analyzed by western blot. 
      Cell location of DIRAS1 in osteosarcoma cells was detected by immunofluorescence. 
      Small interfering RNAs (siRNA)-DIRAS1 and pcDNA3.1-DIRAS1 were employed to 
      regulate DIRAS1 expression. The malignant behaviors of osteosarcoma cells were 
      examined by cell counting kit-8, colony formation, transwell, and wound healing 
      assays. The expression of related proteins was measured by western blot. ELISA 
      and dot blot assays were used to detect the methylation level of m6A. Rescue 
      assays were performed to detect the function of METTL3/METTL14 and DIRASI on 
      osteosarcoma cells. RESULTS: DIRAS1 was located in the nucleus of osteosarcoma 
      cells. Silencing of DIRAS1 in MG63 cells strengthened the proliferation, invasion 
      and migration abilities, as well as blocked the apoptosis ability. Also, p-ERK 
      expression was regulated by DIRAS1 expression, while p-AKT was not affected. 
      Furthermore, DIRAS1 expression was suppressed by METTL3 or/and METTL14 treatment. 
      Moreover, the inhibitory effect of DIRAS1 overexpression on HOS cells malignant 
      behaviors can be reversed by METTL3 and METTL14 joint treatment. The reduced 
      expression of p-ERK induced by DIRAS1 overexpression can be inversed by METTL3 
      and METTL14 co-treatment. CONCLUSIONS: Taken together, our findings illustrated 
      that DIRAS1 regulated by METTL3 and METTL14 can obviously modulate the malignant 
      behaviors of osteosarcoma cells by inactivating ERK pathway.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Liu, Huan
AU  - Liu H
AD  - Department of Osteology, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, Shandong 250012, China.
FAU - Shu, Weibin
AU  - Shu W
AD  - Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to 
      Shandong First Medical University, Jinan, Shandong 250000, China.
FAU - Liu, Tianyue
AU  - Liu T
AD  - Department of Osteology, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, Shandong 250012, China.
FAU - Li, Qingsong
AU  - Li Q
AD  - Second Department of Anesthesiology, The Second Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, Shandong 250012, China.
FAU - Gong, Mingzhi
AU  - Gong M
AD  - Department of Osteology, The Second Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, Shandong 250012, China. Electronic address: 
      Gongmzh242@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20220404
PL  - Scotland
TA  - Tissue Cell
JT  - Tissue & cell
JID - 0214745
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 2.1.1.62 (METTL3 protein, human)
RN  - EC 3.6.1.- (DIRAS1 protein, human)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
SB  - IM
MH  - *Bone Neoplasms/genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - *GTP Phosphohydrolases/metabolism
MH  - Humans
MH  - Methyltransferases/genetics/metabolism
MH  - *Osteosarcoma/genetics/metabolism/pathology
MH  - RNA, Small Interfering/genetics/metabolism
MH  - *Tumor Suppressor Proteins/genetics/metabolism
OTO - NOTNLM
OT  - DIRAS1
OT  - METTL14
OT  - METTL3
OT  - Migration
OT  - Osteosarcoma
OT  - Proliferation
EDAT- 2022/04/13 06:00
MHDA- 2022/06/07 06:00
CRDT- 2022/04/12 20:11
PHST- 2021/10/10 00:00 [received]
PHST- 2022/03/29 00:00 [revised]
PHST- 2022/04/01 00:00 [accepted]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/04/12 20:11 [entrez]
AID - S0040-8166(22)00066-0 [pii]
AID - 10.1016/j.tice.2022.101794 [doi]
PST - ppublish
SO  - Tissue Cell. 2022 Jun;76:101794. doi: 10.1016/j.tice.2022.101794. Epub 2022 Apr 
      4.