Long non-coding RNAs and exosomal lncRNAs: Potential functions in lung cancer progression, drug resistance and tumor microenvironment remodeling

https://doi.org/10.1016/j.biopha.2022.112963Get rights and content
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Highlights

  • Lung cancer is the most malignant tumor in human.

  • Epigenetic alterations mediate lung cancer initiation and progression.

  • Abnormal Long non-coding RNA (lnc) expression results in proliferation, metastasis and therapy resistance in lung cancer.

  • Exosomal lncRNAs are potential diagnostic and prognostic tools.

  • Therapeutic targeting of lncRNAs is effective in lung cancer therapy.

Abstract

Among the different kinds of tumors threatening human life, lung cancer is one that is commonly observed in both males and females. The aggressive behavior of lung cancer and interactions occurring in tumor microenvironment enhances the malignancy of this tumor. The lung tumor cells have demonstrated capacity in developing chemo- and radio-resistance. LncRNAs are a category of non-coding RNAs that do not encode proteins, but their aberrant expression is responsible for tumor development, especially lung cancer. In the present review, we focus on both lncRNAs and exosomal lncRNAs in lung cancer, and their ability in regulating proliferation and metastasis. Cell cycle progression and molecular mechanisms related to lung cancer metastasis such as EMT and MMPs are regulated by lncRNAs. LncRNAs interact with miRNAs, STAT, Wnt, EZH2, PTEN and PI3K/Akt signaling pathways to affect progression of lung cancer cells. LncRNAs demonstrate both tumor-suppressor and tumor-promoting functions in lung cancer. They can be considered as biomarkers in lung cancer and especially exosomal lncRNAs present in body fluids are potential tools for minimally invasive diagnosis. Furthermore, we discuss regulation of lncRNAs by anti-cancer drugs and genetic tools as well as the role of these factors in therapy response of lung cancer cells.

Abbreviations

SCLC
small cell lung cancer
NSCLC
non-small cell lung cancer
miRNA
microRNA
lncRNA
long non-coding RNA
circRNA
circular RNA
EMT
epithelial-to-mesenchymal transition
ncRNAs
non-coding RNAs
mRNA
messenger RNA
ceRNA
competing endogenous RNA
VEGFC
vascular endothelial growth factor C
MDM4
mouse double minute 4
PCD
programmed cell death
EZH2
enhancer of zeste homolog 2
MDSCs
myeloid-derived suppressor cells
CCL5
C-C motif chemokine ligand 5
CAFs
cancer-associated fibroblasts
EGFR
epidermal growth factor receptor
SIRT5
sirtuin 5
CYTOR
cytoskeleton regulator
MMPs
matrix metalloproteinases
TH1
type I helper T
STAT3
signal transducer and activator of transcription factor 3
NF-κB
nuclear factor-kappaB
HK2
hexokinase 2
IL-6
interleukin-6
siRNA
small interfering RNA
shRNA
short hairpin RNA
PI3K
phosphoinositide 3-kinase
Akt
protein kinase-B
PTEN
phosphatase and tensin homolog

Keywords

Lung cancer
Chemoresistance
LncRNA
MiRNA
Radioresistance

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1

These authors have participated equally to manuscript preparation.