PMID- 33125127
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20210917
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 44
IP  - 6
DP  - 2020 Dec
TI  - Aberrant methylation‑mediated decrease of lncRNA HNF1A‑AS1 contributes to 
      malignant progression of laryngeal squamous cell carcinoma via EMT.
PG  - 2503-2516
LID - 10.3892/or.2020.7823 [doi]
AB  - Aberrant methylation is one of the most frequent epigenetic alterations that 
      regulate the expression levels of genes, including long non‑coding RNAs 
      (lncRNAs), in tumors. However, to the best of our knowledge, the expression and 
      function of hepatic nuclear factor 1alpha antisense RNA 1 (HNF1A‑AS1) and its 
      methylation condition have not yet been reported in the development and 
      progression of laryngeal squamous cell carcinoma (LSCC). In the present study, 
      the expression and methylation of HNF1A‑AS1 were first examined by reverse 
      transcription‑quantitative PCR, bisulfite genomic sequencing and 
      methylation‑specific polymerase chain reaction in samples from patients with 
      LSCC, which were based on the in silico analysis using The Cancer Genome Atlas 
      data, and were then further verified in LSCC cell lines with and without 
      5‑Aza‑2'‑deoxycytidine (5‑Aza‑dC) treatment. Subsequently, proliferation, cell 
      cycle distribution, migration and invasion of LSCC cells following either 
      knockdown or overexpression of HNF1A‑AS1 were determined in vitro. Furthermore, 
      the characteristic of HNF1A‑AS1 on epithelial‑mesenchymal transition (EMT) 
      changes was investigated in vitro and in vivo. The associations between the 
      expression levels of HNF1A‑AS1 and tumorigenicity and cervical lymph node 
      metastasis were assessed in a xenograft model in nude mice. In the present study, 
      downregulation and hypermethylation in CpG sites of HNF1A‑AS1 were detected in 
      LSCC tissues as well as metastatic cervical lymph nodes samples when compared 
      with those in the adjacent non‑tumor tissues. Additionally, HNF1A‑AS1 inhibited 
      proliferation, migration and invasion of LSCC cells in vitro by regulating the 
      process of EMT. Furthermore, HNF1A‑AS1 inhibited tumor growth and metastasis by 
      regulating EMT in vivo. Additionally, the migration and invasion abilities, and 
      the expression levels of HNF1A‑AS1 and EMT markers in LSCC cells were 
      significantly reversed by treatment with 5‑Aza‑dC. In summary, HNF1A‑AS1 was 
      downregulated by hypermethylation in LSCC and laryngeal cancer cells. These 
      findings suggested that HNF1A‑AS1 could serve as a tumor suppressor lncRNA in 
      LSCC by regulating the EMT process, leading to the discovery of novel therapeutic 
      targets and strategies for the treatment of patients with LSCC.
FAU - Shi, Yewen
AU  - Shi Y
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Zhang, Qingqing
AU  - Zhang Q
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Xie, Meng
AU  - Xie M
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Feng, Yani
AU  - Feng Y
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Ma, Sijing
AU  - Ma S
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Yi, Chunxi
AU  - Yi C
AD  - Department of Otorhinolaryngology Head and Neck Surgery, Xi'an Central Hospital, 
      Xi'an, Shaanxi 710004, P.R. China.
FAU - Wang, Zihan
AU  - Wang Z
AD  - Department of Otorhinolaryngology Head and Neck Surgery, Xi'an Children's 
      Hospital, Xi'an, Shaanxi 710003, P.R. China.
FAU - Li, Yanju
AU  - Li Y
AD  - Department of Pathology, Yanan University Affiliated Hospital, Yan'an, Shaanxi 
      716000, P.R. China.
FAU - Liu, Xiaohong
AU  - Liu X
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Liu, Haiqin
AU  - Liu H
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Yang, Hui
AU  - Yang H
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Yan, Yan
AU  - Yan Y
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Zhang, Yitong
AU  - Zhang Y
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Ren, Xiaoyong
AU  - Ren X
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
FAU - Luo, Huanan
AU  - Luo H
AD  - Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20201023
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (long non-coding RNA HNF1A-AS1, human)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Azacitidine/pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Chemotherapy, Adjuvant/methods
MH  - CpG Islands
MH  - DNA Methylation/drug effects
MH  - Disease Progression
MH  - Down-Regulation
MH  - Epigenesis, Genetic/drug effects
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Laryngeal Neoplasms/diagnosis/*genetics/pathology/therapy
MH  - Laryngectomy
MH  - Larynx/surgery
MH  - Lymphatic Metastasis/*genetics/pathology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - RNA, Long Noncoding/*genetics/metabolism
MH  - Squamous Cell Carcinoma of Head and Neck/diagnosis/*genetics/pathology/therapy
MH  - Xenograft Model Antitumor Assays
PMC - PMC7640355
OTO - NOTNLM
OT  - lncRNA HNF1A-AS1
OT  - LSCC
OT  - methylation
OT  - EMT
OT  - invasion
EDAT- 2020/10/31 06:00
MHDA- 2021/07/31 06:00
PMCR- 2020/10/23
CRDT- 2020/10/30 12:10
PHST- 2020/03/28 00:00 [received]
PHST- 2020/08/24 00:00 [accepted]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2020/10/30 12:10 [entrez]
PHST- 2020/10/23 00:00 [pmc-release]
AID - or-44-06-2503 [pii]
AID - 10.3892/or.2020.7823 [doi]
PST - ppublish
SO  - Oncol Rep. 2020 Dec;44(6):2503-2516. doi: 10.3892/or.2020.7823. Epub 2020 Oct 23.