PMID- 37424811
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 13
IP  - 6
DP  - 2023
TI  - lncRNA ASBEL and lncRNA Erbb4-IR reduce chemoresistance against gemcitabine and 
      cisplatin in stage IV lung squamous cell carcinoma via the microRNA-21/LZTFL1 
      axis.
PG  - 2732-2750
AB  - Drug resistance is a major cause of treatment failure and post-treatment disease 
      progression in patients with cancer. This study aimed to investigate the 
      mechanisms of chemoresistance to gemcitabine (GEM) plus cisplatin 
      (cis-diamminedichloroplatinum, DDP) combination therapy in stage IV lung squamous 
      cell carcinoma (LSCC). It also examined the functional role of lncRNA ASBEL and 
      lncRNA Erbb4-IR in the malignant progression of LSCC. The expression of lncRNA 
      ASBEL, lncRNA Erbb4-IR, miR-21, and LZTFL1 mRNA was examined in human stage IV 
      LSCC tissues and adjacent normal tissues, human LSCC cells and normal human 
      bronchial epithelial cells using qRT-PCR. Furthermore, LZTFL1 protein levels were 
      also examined using western blots. Cell proliferation, cell migration and 
      invasion, and cell cycle progression and apoptosis were evaluated in vitro using 
      the CCK-8, transwell, and flow cytometry assays, respectively. Based on the 
      treatment response, LSCC tissues were classified as GEM-, DDP-, and 
      GEM+DDP-sensitive/resistant. The MTT assay was performed to assess the 
      chemoresistance of human LSCC cells to GEM, DDP, and GEM+DDP following 
      transfection experiments. The results showed that lncRNA ASBEL, lncRNA Erbb4-IR, 
      and LZTFL1 were down-regulated in human LSCC tissues and cells, whereas miR-21 
      was up-regulated. In stage IV human LSCC tissues, miR-21 levels were negatively 
      correlated with those of lncRNA ASBEL, lncRNA Erbb4-IR, and LZTFL1 mRNA. The 
      overexpression of lncRNA ASBEL and lncRNA Erbb4-IR inhibited cell proliferation, 
      migration, and invasion. It also blocked cell cycle entry and accelerated 
      apoptosis. These effects were mediated by the miR-21/LZTFL1 axis and reduced 
      chemoresistance to GEM+DDP combination therapy in stage IV human LSCC. These 
      findings indicate that lncRNA ASBEL and lncRNA Erbb4-IR function as tumor 
      suppressors in stage IV LSCC and attenuate chemoresistance to GEM+DDP combination 
      therapy via the miR-21/LZTFL1 axis. Hence, lncRNA ASBEL, lncRNA Erbb4-IR, and 
      LZTFL1 may be targeted to enhance the efficacy of GEM+DDP combination 
      chemotherapy against LSCC.
CI  - AJCR Copyright (c) 2023.
FAU - Liang, Zong-Ying
AU  - Liang ZY
AD  - Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical 
      University Chengde, Hebei, China.
FAU - Zhang, Zhi-Min
AU  - Zhang ZM
AD  - Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical 
      University Chengde, Hebei, China.
FAU - Sun, Guang-Rui
AU  - Sun GR
AD  - Department of Education Division, The Affiliated Hospital of Chengde Medical 
      University Chengde, Hebei, China.
FAU - Zhao, Bao-Shan
AU  - Zhao BS
AD  - Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical 
      University Chengde, Hebei, China.
FAU - Xin, Guo-Hua
AU  - Xin GH
AD  - Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical 
      University Chengde, Hebei, China.
FAU - Zhang, Le
AU  - Zhang L
AD  - Department of Thoracic Surgery, The Affiliated Hospital of Chengde Medical 
      University Chengde, Hebei, China.
LA  - eng
PT  - Journal Article
DEP - 20230615
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC10326598
OTO - NOTNLM
OT  - Advanced lung squamous cell carcinoma
OT  - chemoresistance
OT  - gemcitabine and cisplatin combination therapy
OT  - lncRNA ASBEL/lncRNA Erbb4-IR/miR-21/LZTFL1 axis
OT  - tumor suppressor
COIS- None.
EDAT- 2023/07/10 06:42
MHDA- 2023/07/10 06:43
PMCR- 2023/06/15
CRDT- 2023/07/10 04:48
PHST- 2023/02/09 00:00 [received]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2023/07/10 06:43 [medline]
PHST- 2023/07/10 06:42 [pubmed]
PHST- 2023/07/10 04:48 [entrez]
PHST- 2023/06/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2023 Jun 15;13(6):2732-2750. eCollection 2023.