PMID- 38372700
OWN - NLM
STAT- MEDLINE
DCOM- 20240220
LR  - 20240311
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 25
IP  - 1
DP  - 2024 Dec 31
TI  - M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer 
      cells.
PG  - 2306674
LID - 10.1080/15384047.2024.2306674 [doi]
LID - 2306674
AB  - DIRAS family GTPase 1 (DIRAS1) has been reported as a potential tumor suppressor 
      in other human cancer. However, its expression pattern and role in cervical 
      cancer remain unknown. Knockdown of DIRAS1 significantly promoted the 
      proliferation, growth, migration, and invasion of C33A and SiHa cells cultured in 
      vitro. Overexpression of DIRAS1 significantly inhibited the viability and 
      motility of C33A and SiHa cells. Compared with normal cervical tissues, DIRAS1 
      mRNA levels were significantly lower in cervical cancer tissues. DIRAS1 protein 
      expression was also significantly reduced in cervical cancer tissues compared 
      with para-cancerous tissues. In addition, DIRAS1 expression level in tumor 
      tissues was significantly negatively correlated with the pathological grades of 
      cervical cancer patients. DNA methylation inhibitor (5-Azacytidine) and histone 
      deacetylation inhibitor (SAHA) resulted in a significant increase in DIRAS1 mRNA 
      levels in C33A and SiHa cells, but did not affect DIRAS1 protein levels. FTO 
      inhibitor (FB23-2) significantly down-regulated intracellular DIRAS1 mRNA levels, 
      but significantly up-regulated DIRAS1 protein levels. Moreover, the 
      down-regulation of METTL3 and METTL14 expression significantly inhibited DIRAS1 
      protein expression, whereas the down-regulation of FTO and ALKBH5 expression 
      significantly increased DIRAS1 protein expression. In conclusion, DIRAS1 exerts a 
      significant anti-oncogenic function and its expression is significantly 
      downregulated in cervical cancer cells. The m6A modification may be a key 
      mechanism to regulate DIRAS1 mRNA stability and protein translation efficiency in 
      cervical cancer.
FAU - Wang, Yu-Yan
AU  - Wang YY
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou 
      Medical University, Jinzhou, Liaoning, China.
FAU - Ye, Lian-Hua
AU  - Ye LH
AD  - Department of Internal Medicine, Zigong Fourth People's Hospital, Zigong, 
      Sichuan, China.
FAU - Zhao, An-Qi
AU  - Zhao AQ
AD  - Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical 
      University, Beijing, China.
FAU - Gao, Wei-Ran
AU  - Gao WR
AD  - Department of Oncology, The First Affiliated Hospital of Jinzhou Medical 
      University, Jinzhou, Liaoning, China.
FAU - Dai, Ning
AU  - Dai N
AD  - Department of Oncology, The First Affiliated Hospital of Jinzhou Medical 
      University, Jinzhou, Liaoning, China.
FAU - Yin, Yu
AU  - Yin Y
AD  - Operating Rooms, The First Affiliated Hospital of Jinzhou Medical University, 
      Jinzhou, Liaoning, China.
FAU - Zhang, Xin
AU  - Zhang X
AUID- ORCID: 0000-0001-5966-2744
AD  - Department of Oncology, The First Affiliated Hospital of Jinzhou Medical 
      University, Jinzhou, Liaoning, China.
LA  - eng
PT  - Journal Article
DEP - 20240219
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - W7IBY2BGAX (6-methyladenine)
RN  - JAC85A2161 (Adenine)
RN  - M801H13NRU (Azacitidine)
RN  - 0 (RNA, Messenger)
RN  - EC 2.1.1.62 (METTL3 protein, human)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 3.6.1.- (DIRAS1 protein, human)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 1.14.11.33 (FTO protein, human)
RN  - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Uterine Cervical Neoplasms/genetics
MH  - Adenine/*analogs & derivatives
MH  - Azacitidine/pharmacology
MH  - RNA, Messenger/genetics
MH  - Methyltransferases
MH  - GTP Phosphohydrolases
MH  - Tumor Suppressor Proteins
MH  - Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PMC - PMC10878024
OTO - NOTNLM
OT  - Cervical cancer
OT  - DIRAS1
OT  - epigenetic regulation
OT  - m6A
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2024/02/19 12:42
MHDA- 2024/02/20 11:51
PMCR- 2024/02/19
CRDT- 2024/02/19 10:43
PHST- 2024/02/20 11:51 [medline]
PHST- 2024/02/19 12:42 [pubmed]
PHST- 2024/02/19 10:43 [entrez]
PHST- 2024/02/19 00:00 [pmc-release]
AID - 2306674 [pii]
AID - 10.1080/15384047.2024.2306674 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2024 Dec 31;25(1):2306674. doi: 10.1080/15384047.2024.2306674. 
      Epub 2024 Feb 19.