PMID- 36958438
OWN - NLM
STAT- MEDLINE
DCOM- 20230411
LR  - 20230411
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 321
DP  - 2023 May 15
TI  - LncRNA HHIP-AS1 suppresses lung squamous cell carcinoma by stabilizing HHIP mRNA.
PG  - 121578
LID - S0024-3205(23)00212-6 [pii]
LID - 10.1016/j.lfs.2023.121578 [doi]
AB  - AIMS: Lung squamous cell carcinoma (LUSC) causes over 400,000 deaths annually, 
      yet it lacks targeted therapy. A major antagonist of Hedgehog pathway, HHIP 
      (Hedgehog Interacting Protein) plays an important role in LUSC; however, the 
      regulatory mechanism remains unclear. Long non-coding RNA HHIP-AS1 plays 
      suppressive or promotive roles in different cancers, but its role in LUSC remains 
      unknown. This manuscript is to investigate regulatory mechanism of HHIP and the 
      role of HHIP-AS1 in LUSC. MAIN METHODS: Precision-cut lung slices (PCLS) from 
      human LUSC samples are cultured to mimic LUSC growth. Overexpression and 
      knockdown in multiple LUSC cell lines and PCLS are achieved by lentivirus 
      infection. Transcriptome profile and lung cancer activity are evaluated by 
      RNA-sequencing, immunostaining and CCK8 assay etc. KEY FINDINGS: HHIP is 
      regulated independently of Hh pathway in LUSC. Additionally, downregulation of 
      HHIP-AS1 is associated with poor prognosis. Consistently, HHIP-AS1 inhibits LUSC 
      growth by suppressing cell proliferation and migration. Transcriptome profiling 
      of HHIP-AS1 knockdown (KD) cells uncovered HHIP downregulation. Interestingly, a 
      comparison between the transcriptomes of HHIP-AS1 KD or HHIP KD cells manifested 
      high similarity. Subsequently it's confirmed that HHIP-AS1 regulates HHIP in LUSC 
      cells. Notably, HHIP-AS1 regulation on LUSC growth is achieved through 
      stabilizing HHIP mRNA rather than regulating MIR-153-3P/PCDHGA9 or 
      MIR-425-5P/DNYC1I2. Finally, it's confirmed in PCLS from human LUSC samples that 
      HHIP-AS1 suppresses LUSC via regulating HHIP mRNA. SIGNIFICANCE: This study 
      uncovers HHIP-AS1 as a novel tumor suppressor in LUSC and provides new insights 
      into the molecular regulation of LUSC, which will help developing new therapeutic 
      strategies.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Hu, Zheyu
AU  - Hu Z
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China.
FAU - Liu, Yixian
AU  - Liu Y
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China.
FAU - Tang, Jin
AU  - Tang J
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China.
FAU - Luo, Renru
AU  - Luo R
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China.
FAU - Qin, Jiajia
AU  - Qin J
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China.
FAU - Mo, Zexun
AU  - Mo Z
AD  - Department of Pulmonary and Critical Care Medicine, Guangzhou First People's 
      Hospital, School of Medicine, South China University of Technology, 1 Panfu Road, 
      Guangzhou 510180, China.
FAU - Xie, Jianjiang
AU  - Xie J
AD  - Department of Thoracic Surgery, Guangzhou First People's Hospital, School of 
      Medicine, South China University of Technology, Guangzhou 510180, China.
FAU - Jiang, Xuan
AU  - Jiang X
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China.
FAU - Wei, Shuquan
AU  - Wei S
AD  - Department of Pulmonary and Critical Care Medicine, Guangzhou First People's 
      Hospital, School of Medicine, South China University of Technology, 1 Panfu Road, 
      Guangzhou 510180, China. Electronic address: eyweishuquan@scut.edu.cn.
FAU - Lin, Chuwen
AU  - Lin C
AD  - Department of histology and embryology, School of Medicine, Shenzhen Campus of 
      Sun Yat-sen University, Sun Yat-sen University, 66 Gongchang Road, Shenzhen 
      518107, China. Electronic address: linchw8@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230321
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (HHIP protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (MIRN153 microRNA, human)
SB  - IM
MH  - Humans
MH  - *MicroRNAs/genetics
MH  - *RNA, Long Noncoding/genetics
MH  - RNA, Messenger/genetics
MH  - Hedgehog Proteins/genetics
MH  - Cell Line, Tumor
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - *Carcinoma, Squamous Cell/genetics/pathology
MH  - *Lung Neoplasms/genetics/pathology
MH  - Cell Proliferation/genetics
MH  - Lung/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Cell Movement/genetics
MH  - Carrier Proteins/genetics
MH  - Membrane Glycoproteins/genetics
OTO - NOTNLM
OT  - HHIP
OT  - HHIP-AS1
OT  - LUSC
OT  - PCLS
COIS- Declaration of competing interest The authors report no conflicts of interest in 
      this work.
EDAT- 2023/03/24 06:00
MHDA- 2023/04/11 06:41
CRDT- 2023/03/23 20:28
PHST- 2023/01/14 00:00 [received]
PHST- 2023/03/04 00:00 [revised]
PHST- 2023/03/13 00:00 [accepted]
PHST- 2023/04/11 06:41 [medline]
PHST- 2023/03/24 06:00 [pubmed]
PHST- 2023/03/23 20:28 [entrez]
AID - S0024-3205(23)00212-6 [pii]
AID - 10.1016/j.lfs.2023.121578 [doi]
PST - ppublish
SO  - Life Sci. 2023 May 15;321:121578. doi: 10.1016/j.lfs.2023.121578. Epub 2023 Mar 
      21.