PMID- 35710093
OWN - NLM
STAT- MEDLINE
DCOM- 20220713
LR  - 20220817
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 543
DP  - 2022 Sep 1
TI  - Down-regulation of circPTTG1IP induces hepatocellular carcinoma development via 
      miR-16-5p/RNF125/JAK1 axis.
PG  - 215778
LID - S0304-3835(22)00262-2 [pii]
LID - 10.1016/j.canlet.2022.215778 [doi]
AB  - Circular RNAs are known to regulate the biological processes of hepatocellular 
      carcinoma (HCC), and humans with Down syndrome are at low risk of developing 
      solid tumors due to the amplification of several tumor suppressor genes on human 
      chromosome 21 (HSA21). Here, we aimed to investigate the potential role of 
      circRNAs originating from HSA21 in the progression of HCC. CircRNA-sequencing was 
      performed to analyze differentially expressed circRNAs in 4 HCC and peritumor 
      tissues, and circRNAs originating from HSA21 were further analyzed. Circ_0061984 
      (circPTTG1IP) was chosen for further study because it showed the lowest 
      expression in HCC tissues, and qRT-PCR was used to confirm the expression of 
      circPTTG1IP in HCC patient tissues. The biological function of circPTTG1IP was 
      detected in HCC cells both in vivo and in vitro. Moreover, luciferase reporter 
      assays, circRNA immunoprecipitation, and fluorescence in situ hybridization 
      (FISH) were used to investigate the potential mechanism of circPTTG1IP. Finally, 
      the possible mechanisms of filgotinib in circPTTG1IP-driven HCC were assessed. 
      CircPTTG1IP expression was decreased in HCC compared to peritumoral tissues. 
      Moreover, low circPTTG1IP expression was revealed to be associated with a poor 
      prognosis of HCC patients. Elevation of circPTTG1IP was revealed to inhibit HCC 
      development both in vitro and in vivo. Mechanistically, circPTTG1IP was shown to 
      function as a competing endogenous RNA (ceRNA) of RNF125 by binding miR-16-5p to 
      increase the level of the E3 ubiquitin ligase RNF125, which further ubiquitinated 
      and degraded JAK1 protein. Finally, we demonstrated that administration of 
      filgotinib, a JAK1 inhibitor, restricted HCC progression induced by low 
      circPTTG1IP expression. Thus, we revealed that circPTTG1IP is a novel tumor 
      suppresser circRNA in HCC and that a low circPTTG1IP level promotes HCC 
      development via the miR-16-5p/RNF125/JAK1 axis. Patients with low circPTTG1IP may 
      benefit from filgotinib treatment.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Peng, Rui
AU  - Peng R
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Cao, Jun
AU  - Cao J
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Su, Bing-Bing
AU  - Su BB
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Bai, Xue-Song
AU  - Bai XS
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Jin, Xin
AU  - Jin X
AD  - Biobank, Clinical Medical College, Yangzhou University, Northern Jiangsu People's 
      Hospital, Yangzhou, China.
FAU - Wang, Ao-Qing
AU  - Wang AQ
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Liu, Ren-Jie
AU  - Liu RJ
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Jiang, Guo-Qing
AU  - Jiang GQ
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Jin, Sheng-Jie
AU  - Jin SJ
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China.
FAU - Zhang, Chi
AU  - Zhang C
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China. Electronic address: 
      18051062769@yzu.edu.cn.
FAU - Bai, Dou-Sheng
AU  - Bai DS
AD  - Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou 
      University, Yangzhou, 225009, Jiangsu, China. Electronic address: 
      drbaidousheng@yzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220613
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (MIRN16 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - *Carcinoma, Hepatocellular/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Down-Regulation
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Janus Kinase 1/genetics
MH  - *Liver Neoplasms/pathology
MH  - *MicroRNAs/metabolism
MH  - RNA, Circular/genetics
OTO - NOTNLM
OT  - Biomarker
OT  - Hepatocellular carcinoma
OT  - Tumor suppressor
OT  - Ubiquitination
OT  - circRNA
EDAT- 2022/06/17 06:00
MHDA- 2022/07/14 06:00
CRDT- 2022/06/16 19:35
PHST- 2022/01/30 00:00 [received]
PHST- 2022/06/01 00:00 [revised]
PHST- 2022/06/01 00:00 [accepted]
PHST- 2022/06/17 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/06/16 19:35 [entrez]
AID - S0304-3835(22)00262-2 [pii]
AID - 10.1016/j.canlet.2022.215778 [doi]
PST - ppublish
SO  - Cancer Lett. 2022 Sep 1;543:215778. doi: 10.1016/j.canlet.2022.215778. Epub 2022 
      Jun 13.