PMID- 33414996
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210111
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 10
IP  - 12
DP  - 2020
TI  - Identification of DHX36 as a tumour suppressor through modulating the activities 
      of the stress-associated proteins and cyclin-dependent kinases in breast cancer.
PG  - 4211-4233
AB  - The nucleic acid guanine-quadruplex structures (G4s) are involved in many aspects 
      of cancer progression. The DEAH-box polypeptide 36 (DHX36) has been identified as 
      a dominant nucleic acid helicase which targets and disrupts DNA and RNA G4s in an 
      ATP-dependent manner. However, the actual role of DHX36 in breast cancer remains 
      unknown. In this study, we observed that the gene expression of DHX36 was 
      positively associated with patient survival in breast cancer. The abundance of 
      DHX36 is also linked with pathologic conditions and the stage of breast cancer. 
      By using the xenograft mouse model, we demonstrated that the stable knockdown of 
      DHX36 via lentivirus in breast cancer cells significantly promoted tumour growth. 
      We also found that, after the DHX36 knockdown (KD), the invasion of 
      triple-negative breast cancer cells was enhanced. In addition, we found a 
      significant increase in the number of cells in the S-phase and a reduction of 
      apoptosis with the response to cisplatin. DHX36 KD also desensitized the 
      cytotoxic cellular response to paclitaxel and cisplatin. Transcriptomic profiling 
      analysis by RNA sequencing indicated that DHX36 altered gene expression profile 
      through the upstream activation of TNF, IFNgamma, NFkappab and TGFbeta1. High throughput 
      signalling analysis showed that one cluster of stress-associated kinase proteins 
      including p53, ROCK1 and JNK were suppressed, while the mitotic checkpoint 
      protein-serine kinases CDK1 and CDK2 were activated, as a consequence of the 
      DHX36 knockdown. Our study reveals that DHX36 functions as a tumour suppressor 
      and may be considered as a potential therapeutic target in breast cancer.
CI  - AJCR Copyright (c) 2020.
FAU - Zeng, Yinduo
AU  - Zeng Y
AD  - Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou 
      510120, China.
AD  - Cardiff China Medical Research Collaborative, Cardiff University School of 
      Medicine Heath Park, Cardiff CF14 4XN, UK.
AD  - Breast Tumour Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University 
      Guangzhou 510120, China.
FAU - Qin, Tao
AU  - Qin T
AD  - Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou 
      510120, China.
AD  - Department of Medical Oncology, Sun Yat-sen Memorial Hospital of Sun Yat-sen 
      University Guangzhou, China.
FAU - Flamini, Valentina
AU  - Flamini V
AD  - Cardiff China Medical Research Collaborative, Cardiff University School of 
      Medicine Heath Park, Cardiff CF14 4XN, UK.
FAU - Tan, Cui
AU  - Tan C
AD  - Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou 
      510120, China.
AD  - Department of Pathology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University 
      Guangzhou, China.
FAU - Zhang, Xinke
AU  - Zhang X
AD  - Sun Yat-sen University Cancer Centre, The State Key Laboratory of Oncology in 
      South China, Collaborative Innovation Centre for Cancer Medicine Guangzhou 
      510060, China.
FAU - Cong, Yizi
AU  - Cong Y
AD  - Cardiff China Medical Research Collaborative, Cardiff University School of 
      Medicine Heath Park, Cardiff CF14 4XN, UK.
AD  - Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of 
      Qingdao University Yantai, China.
FAU - Birkin, Emily
AU  - Birkin E
AD  - Cardiff China Medical Research Collaborative, Cardiff University School of 
      Medicine Heath Park, Cardiff CF14 4XN, UK.
FAU - Jiang, Wen G
AU  - Jiang WG
AD  - Cardiff China Medical Research Collaborative, Cardiff University School of 
      Medicine Heath Park, Cardiff CF14 4XN, UK.
FAU - Yao, Herui
AU  - Yao H
AD  - Guangdong Provincial Key Laboratory of Malignant Tumour Epigenetics and Gene 
      Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou 
      510120, China.
AD  - Breast Tumour Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University 
      Guangzhou 510120, China.
FAU - Cui, Yuxin
AU  - Cui Y
AD  - Cardiff China Medical Research Collaborative, Cardiff University School of 
      Medicine Heath Park, Cardiff CF14 4XN, UK.
LA  - eng
PT  - Journal Article
DEP - 20201201
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC7783738
OTO - NOTNLM
OT  - CDK
OT  - DHX36
OT  - breast cancer
OT  - progression
OT  - stress-associated protein
COIS- None.
EDAT- 2021/01/09 06:00
MHDA- 2021/01/09 06:01
PMCR- 2020/12/01
CRDT- 2021/01/08 06:12
PHST- 2020/09/25 00:00 [received]
PHST- 2020/11/29 00:00 [accepted]
PHST- 2021/01/08 06:12 [entrez]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/01/09 06:01 [medline]
PHST- 2020/12/01 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2020 Dec 1;10(12):4211-4233. eCollection 2020.