PMID- 32308748
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20231213
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 10
IP  - 11
DP  - 2020
TI  - Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism 
      of non-small cell lung cancer by regulating PKM2/HIF-1alpha axis.
PG  - 4762-4778
LID - 10.7150/thno.43839 [doi]
AB  - Rationale: Non-small cell lung cancer (NSCLC) is a deadly disease with a hallmark 
      of aberrant metabolism. The mechanism of glycolysis associated lncRNA underlying 
      the aggressive behaviors of NSCLC is poorly understood. Methods: The expression 
      level of AC020978 in NSCLC was measured by quantitative real-time PCR and 
      fluorescence in situ hybridization (FISH) assay. The biological role of AC020978 
      in cell proliferation and aerobic glycolysis was determined by functional 
      experiments in vitro and in vivo. The transcription of AC020978 was assessed by 
      dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assay. RNA 
      pull-down, mass spectrometry and RNA immunoprecipitation (RIP) assays were used 
      to identify the interaction protein with AC020978. Western blotting, in situ 
      proximity ligation assay (PLA), and co-immunoprecipitation (co-IP) were performed 
      to reveal the potential mechanism of AC020978. Results: The present study 
      indicated that AC020978 was upregulated in NSCLC, significantly correlated with 
      advanced TNM stage and poor clinical outcomes, representing as an independent 
      prognostic predictor. Functional assays revealed AC020978's role in promoting 
      cell growth and metabolic reprogramming. Moreover, AC020978 was an upregulated 
      lncRNA under glucose starvation as well as hypoxia conditions, and directly 
      transactivated by HIF-1alpha. Mechanistic investigations identified that AC020978 
      directly interacted with Pyruvate kinase isozymes M2 (PKM2) and enhanced PKM2 
      protein stability. Besides, this study uncovered that AC020978 could promote the 
      nuclear translocation of PKM2 and regulate PKM2-enhanced HIF-1alpha transcription 
      activity. Conclusions: Together, these data provided evidence that AC020978 
      conferred an aggressive phenotype to NSCLC and was a poor prognosticator. 
      Targeting AC020978 might be an effective therapeutic strategy for NSCLC.
CI  - (c) The author(s).
FAU - Hua, Qian
AU  - Hua Q
AD  - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai 200127, China.
FAU - Mi, Baoming
AU  - Mi B
AD  - Department of Nuclear Medicine, The second Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215004, China.
FAU - Xu, Fei
AU  - Xu F
AD  - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai 200127, China.
FAU - Wen, Jun
AU  - Wen J
AD  - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai 200127, China.
FAU - Zhao, Li
AU  - Zhao L
AD  - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai 200127, China.
FAU - Liu, Jianjun
AU  - Liu J
AD  - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai 200127, China.
FAU - Huang, Gang
AU  - Huang G
AD  - Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiaotong University, Shanghai 200127, China.
AD  - Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and 
      Health Sciences, Shanghai 201318, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200326
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (Carrier Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Thyroid Hormones)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/pathology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Hypoxia/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/physiology
MH  - Glycolysis
MH  - Heterografts
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Lung Neoplasms/genetics/*metabolism/pathology
MH  - Male
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Staging
MH  - RNA, Long Noncoding/*genetics
MH  - Signal Transduction
MH  - Survival Rate
MH  - Thyroid Hormones/genetics/*metabolism
MH  - Up-Regulation
MH  - Thyroid Hormone-Binding Proteins
PMC - PMC7163453
OTO - NOTNLM
OT  - AC020978
OT  - HIF-1alpha
OT  - Long noncoding RNAs
OT  - PKM2
OT  - aerobic glycolysis
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2020/04/21 06:00
MHDA- 2021/05/14 06:00
PMCR- 2020/01/01
CRDT- 2020/04/21 06:00
PHST- 2020/01/10 00:00 [received]
PHST- 2020/03/07 00:00 [accepted]
PHST- 2020/04/21 06:00 [entrez]
PHST- 2020/04/21 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - thnov10p4762 [pii]
AID - 10.7150/thno.43839 [doi]
PST - epublish
SO  - Theranostics. 2020 Mar 26;10(11):4762-4778. doi: 10.7150/thno.43839. eCollection 
      2020.