Page 43 - Read Online

Page 167 Kamal et al. J Transl Genet Genom 2024;8:162-85 https://dx.doi.org/10.20517/jtgg.2023.55

Post-transcriptional regulation of lncRNAs can also involve collaborative mechanisms that enhance the
stability of two or more lncRNAs. A notable example is the collaborative action observed between lncRNAs
MALAT1 and MENβ, forming a protective triple helix that shields these transcripts from exonuclease
damage [43,44] .

The stability of lncRNAs can also be influenced by the types and contents of nucleotides they contain. For
example, lncRNAs encompass more than 100 distinct modified nucleotides beyond the four core
nucleotides found in RNAs. Similar modified nucleotides are present in other short non-coding RNAs such
as rRNAs, tRNAs, and small nuclear RNAs and contribute to the stability of these ncRNAs, including
lncRNAs . Interestingly, the secondary structures of lncRNAs can serve as substrates for the adenosine
[45]
deaminase enzyme, catalyzing Adenosine to Inosine (A-to-I) conversion in an RNA editing process. These
[46]
edited lncRNAs may undergo different processes, including RNA degradation .

LncRNAs IN MEDICINE
LncRNAs, with their involvement in various physiological functions and distinct tissue and cell-specific
expression, play a pivotal role in the pathology and potential treatment of various diseases [Figure 3]. Here,
we briefly highlight a few instances of their involvement as pathological or biological markers (biomarkers)
and their potential applications in treatment approaches.

LncRNAs as biomarkers
A biomarker, a biological molecule presents in blood, other bodily fluids, or tissues, serves as an indicator of
normal or abnormal processes, conditions, or diseases. Biomarkers are crucial for assessing how effectively
the body responds to treatments and the current diagnostic state of any disease . In the specific context of
[47]
lncRNAs, they can be regarded as biomarkers owing to their tissue-specific genetic characteristics, enabling
lncRNAs to elucidate the distinct functions of tissues, making them valuable markers specific to particular
tissues and diseases [26,28] .

Brain injury
Brain injuries, such as traumatic brain injury (TBI), can result in chronic disabilities and a reduction in
survival rate, making them significant health problems [48-50] . TBIs cause acute brain damage in which blood
vessels, neurons, and glia stretch or rupture, causing apoptosis and harming the Blood-Brain Barrier.
Afterwards, a pro-inflammatory immune response takes place, which causes phagocytosis of dead and
injured cells and the secretion of pro-inflammatory cytokines. Chronic inflammation results if this immune
response is not resolved in moderate to severe injuries, and its complications can last for weeks to years
after injury [48,49,51] . A study conducted by Wang et al. discovered a group of 271 differentially expressed
lncRNAs in the rat hippocampus following TBI, and these lncRNAs were associated with several biological
[52]
functions, including inflammatory responses and apoptosis . Another study on mice discovered 823
[53]
abnormally expressed lncRNAs, with 156 downregulated and 667 upregulated genes . In human subjects,
Yang et al. investigated the expression of lncRNAs in three different human patients diagnosed with TBI,
and the results indicated 56 downregulated and 43 upregulated lncRNAs .
[54]

Spinal cord injury
Spinal cord injury (SCI) is a devastating disorder of the central nervous system that often leads to the loss of
motor and sensory functions, with an incidence rate that ranges from 3.6 to 195.4 cases per million
worldwide . The two leading causes of SCI are falls and accidents . SCI, however, can also result from
[56]
[55]
non-traumatic diseases such as inflammatory wounds, poor blood supply, osteoarthritis, and spinal
[57]
tumors . Paralysis, sensory impairment, neuropathic pain, and other dysfunctions are common among