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Global Translational Medicine Risk factors of idiopathic pulmonary fibrosis

HOXA expression was observed in breast, stomach, Table 2. Molecular targets of lncRNAs and their effect on
pancreatic cancer, and hepatocellular carcinoma ; lung fibrosis
[40]
lncRNA LUCAT1 was observed in breast, ovarian, LncRNA Molecular targets Effect
thyroid cancer, and renal cell carcinoma ; and lncRNA
[41]
MALAT1 was observed in cancer of the breast, prostate, PFAR [3] miR-138 Profibrotic
colon, liver, and uterus , etc. An association was found MALAT1 [4] miR-503
[37]
between increased expression of lncRNA TP53TG1 and Н19 [50-52] miR-29b
increased migration and proliferation of hepatocellular miR-196a
carcinoma cells , progression of retinoblastoma (by miR-140
[42]
miR-33b [miRNA-33b] binding) , and development hsa-miR-196
[43]
of pancreatic duct adenocarcinoma . Activation of MEG3 [53] TP63, STAT3, KRT14, YAP1, AXL, TP53,
[44]
lncRNA LINC00342 resulted in inhibition of miR-545-5p, EZH2, TGF-β genes
subsequent overexpression of CNPY2, and progression TERRA [54] Telomerase
of gastric cancer . A study of Shen et al. observed an [55]
[45]
[46]
association between increased expression of LINC00342, PVT1 miR-497-5p
sequestration of miR-19a-3p, and progression of colorectal HOXAAS3 [56] miR-450b-5p
cancer. Chen et al. found an increase in LINC00342 PFAL [57] miR-18a
[47]
expression in non-small cell lung cancer tissue; the DNM3OS [58] Predecessor of miR199a-5p/3p,
binding of this lncRNA to miR-203a-3p led to increased miR-214-3p
cell proliferation, migration, and invasion. Furthermore, ZFAS1 [59] miR-150-5p Antifibrotic
LINC00342 overexpression and miR-384 binding led to FENDRR [51] hsa-miR-214
[48]
the development of thyroid cancer . In turn, in gastric Aconitase 1
cancer, a decrease in lncRNA RP11-363E7.4 expression is DNM3OS: DNM3 (Dynamine 3) opposite strand/antisense
observed, and functional experiments performed by Chen RNA, FENDRR: FOXF1 (Forkhead Box F1) adjacent non-coding
et al. showed the presence of antitumor activity during developmental regulatory RNA, H19:H19 imprinted maternally
[49]
overexpression of this lncRNA when it affects the signaling expressed transcript, HOXAAS3:HOXA (Homeobox A
pathways tp53, Bax/Bcl-2, and β-catenin. Cluster) antisense RNA 3, MALAT1:metastasis-associated lung
adenocarcinoma transcript 1, MEG3: Maternally expressed 3,
3.4.3. LncRNAs in pulmonary fibrosis pathogenesis PFAL: Pulmonary fibrosis-associated lncRNA, PFAR: Pancreatic
fibrosis-associated lncRNA, PVT1: Plasmacytoma variant translocation
There are studies confirming the role of lncRNA in the 1, TERRA: Telomeric-repeat-containing RNA, ZFAS1: ZNFX1
development of pulmonary fibrosis (Table 2). Overexpression (Zinc Finger NFX1-Type Containing 1) antisense RNA 1
of lncRNA PFAR was observed in a mouse model of
bleomycin-induced pulmonary fibrosis, with PFAR being final differentiation, which can affect tissue remodeling
[53]
the competing endogenous RNA (ceRNA) for miR-138. in IPF . Lnc TERRA contains telomerase sequences and
Knockdown of PFAR caused attenuation of TGF-β1-induced reduces telomerase activity. This leads to mitochondrial
fibrosis . Yan et al. demonstrated the antifibrotic role of dysfunction in alveolar epitheliocytes, thereby contributing
[3]
[54]
miR-503 in pulmonary silicosis and the profibrotic role of to fibrosis . FENDRR can inhibit fibroblast activation and
lncRNA MALAT1 (ceRNA for miR-503) . The miR-29b- reduce pulmonary fibrosis by taking up aconitase 1, thereby
[4]
binding H19 expression was reported to be upregulated reducing iron levels and sequestering profibrotic hsa-
[51]
in mice with bleomycin-induced pulmonary fibrosis, miR-214 . LncRNA PVT1, which sequesters miR-497-5p,
[55]
which was accompanied by an increase in the expression has a profibrotic effect in mouse models with lung silicosis .
of COL1A1 (responsible for the synthesis of the collagen I LncRNA Hoxaas3 induced by TGF-β1/SMAD 4 signaling
alpha-1 chain). Furthermore, H19 bound miR-196a and pathway promotes the activation of fibroblasts and EMT by
[56]
miR-140 in vitro and in vivo, which led to the progression of inhibiting the action of miR-450b-5p . LncRNA PFAL was
TGF-β1- and bleomycin-induced fibrosis . An analysis of found to have profibrotic activity, which manifested itself
[50]
the role of some lncRNAs in the development of lung diseases upon the inhibition of miR-18a. There was an increase in
yielded findings as follows: H19 sequesters hsa-miR-140 to migration, proliferation of fibroblasts, EMT, and synthesis
cause an increase in the expression of TGF-β1 and sequester of intercellular substance, which was proven in laboratory
hsa-miR-196 to enhance the proliferation and migration of mice with pulmonary fibrosis and activated by TGF-β1
fibroblasts [51,52] . MEG3 upregulates TP63, STAT3, KRT14, fibroblast as shown in cell culture experiments . LncRNA
[57]
YAP1, AXL, TP53, EZH2, and TGF-β genes to promote the DNM3OS, whose expression is activated by both TGF-
migration of young alveolar epitheliocytes and prevent their β1- and Wnt-mediated signaling pathways is the precursor

Volume 1 Issue 2 (2022) 6 https://doi.org/10.36922/gtm.v1i2.107