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Kamal et al. J Transl Genet Genom 2024;8:162-85 https://dx.doi.org/10.20517/jtgg.2023.55 Page 170

LncRNAs as potential therapeutic approaches
Brain injury
As previously mentioned, lncRNAs can be differentially expressed in brains following TBI, affecting many
biological processes that follow brain injuries. Zhong et al. investigated the differentially expressed lncRNA
NEAT1 through knockdown experiments in mice and found that NEAT1 was found to decrease the
[89]
number of cells undergoing apoptosis and decrease the intensity of inflammation . In a study by
Patel et al., exosomes, extracted from human adipose-derived stem cells (hASCs), were injected into rats
following TBI. Those exosomes were tested against lncRNA MALAT1-depleted exosomes, and the results
indicated the role of MALAT1 in the improvement and recovery of TBI-related symptoms .
[90]

Spinal cord injury
As a promising therapeutic strategy, neural stem cells have been proposed as a potential solution . It has
[91]
been shown that the lncRNA UCA1 controls the differentiation and proliferation of neural stem cells, and
[92]
therefore, it can have a huge impact on the treatment of SCI . Another interesting study has shown that
hydrogen sulfide, a potential treatment for SCI, has an impact on the upregulation of lncRNA CasC7, which
[93]
results in decreasing the apoptosis of neuronal cells and improving SCI .

Alzheimer's disease
Gene silencing with siRNAs is a method of knocking down genes that results in gene expression
regulation . The introduction of siRNAs, which target the lncRNA BACE1-AS, into the transgenic AD
[94]
[95]
mouse brains reduced the expression of both BACE1-AS and BACE1 . This approach poses the question
of whether the same can be applied to many other dysregulated lncRNAs that are involved in many
pathophysiological pathways.

Huntington's disease
One of the repressed genes in HD is the protein Brain-Derived Neurotrophic Factor (BDNF) . BDNF
[96]
enhances the survival of the neurons and their cytoskeleton rearrangement, providing neuroprotection
during inflammation . It has been hypothesized that the loss of BDNF may explain the loss of neurons
[97]
where mutant Huntingtin protein is ubiquitously expressed [98,99] . The presence of lncRNA BDNF-AS has
been found to decrease the expression and function of the BDNF protein via chromatin modification at the
[100]
BDNF gene location and thus suppress the expression of the BDNF transcript . Therefore, studying the
expression of lncRNA BDNF-AS in HD may be a promising point that can be used for the design of a
therapeutic approach for HD.

Prostate cancer
The potential therapeutic effects of lncRNAs in prostate cancer have been growing recently. A recent study
has shown that the lncRNA DNMBP-AS1, which is upregulated in prostate cancer, is capable of inducing
the cellular proliferation and metastasis of prostate cancer cells via sponging of miR-6766-3p. Knocking
[101]
down this lncRNA has led to the inhibition of cancer cell proliferation and metastasis . Another earlier
study investigated the effect of the overexpression of already downregulated lncRNAs; this study has shown
that the upregulation of the expression of the lncRNA MIR22HG in prostate cancer cells, which resulted in
[102]
the sequestration of miR-9-3p, led to the inhibition of apoptosis and cancer cell proliferation .

Breast cancer
It has been shown that the downexpression of lncRNA PANDAR, using a siRNA-based technique, led to a
reduction in the cellular growth of in vitro breast cancer cells and increased the number of cells within the
[83]
G1 phase . Another interesting study by Ren et al. discovered that inhibition of TGF-β1 along with other