Introduction: Although great research has been done to clarify the pathogenesis of colorectal cancer (CRC), it is still the third
common cancer worldwide. Pathogenesis of CRC as a heterogeneous disease is correlated with mutations and
epigenetic alterations that result in the inactivation of tumor-suppressive and activation of an oncogene. Small
non-coding RNAs (sncRNAs), emerging as a key player in regulating the genes and protein expression, with a
length less than 200 nucleotide (nt). In this review, we aimed to focus on the role and the biogenesis of PIWIinteracting RNA (piRNAs), and tRNA-derived small RNA (tRFs) and PIWI proteins in the initiation, progression,
and metastasis of CRC and their molecular mechanisms to understand their function in cancers and to provide
better therapeutic strategies for CRC.
Methods: Recently with the help of new sequencing a huge number of snRNAs
have been discovered and many of them are indicated as biomarkers and
prognostic factors based on their gene regulatory function both in the
nucleus and in the cytoplasm. However, only a small number of them are
available as therapeutic tools. Previous have uncovered the important
roles of sncRNAs in gene regulation and other cellular processes related
to initiation, progression of tumors and different response to chemotherapy and radiotherapy treatments. The expression patterns of
sncRNAs are very in different tumor tissues compared to the corresponding normal tissue and some of them have show a close association
with tumor stages and metastasis. For examole, piR-5937 and piR28,876 expression were decreased significantly in serum of patients
with colorectal cancer and correlating with clinical stage I, suggesting as
promising biomarkers for early CRC detection [50,51]. PIWIL2 expression was positively associated with CRC and was related to various
clinic-pathologic parameters and a poor prognosis [35]. Therefore small
non-coding RNAs can be used as new biological markers for the early
detection of CRC due to their stability abundance tissues, nominated as
an attractive prognostic and diagnostic biomarker candidate [26,31,32].
However our understanding of this field remains incomplete and their
mechanism in cellular signaling pathways and animal models needs
more investigations. New studies have aimed into the employment of
ncRNA in lipid nano-particles as new therapeutic strategies for delivery.
The application for novel sncRNAs is so rare and there are many new
challenges to overcome before their widely applications. The reason
might be due to several factors. First, is based on the difficulty of targeting specific genes due to their short sequence, they might regulate
several target genes non-specifically. Second, the optimal system for
delivering sncRNAs has not been fully established yet, therefore better
understanding about the role of sncRNAs will pave a new ways in their
therapeutic application in CRC treatment.
Results: Not applicable
Ethics approval and consent to participate
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Consent for publication
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Availability of data and materials
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CRediT authorship contribution statement
Mandana AmeliMojarad: Writing – original draft. Melika AmeliMojarad: Writing – review & editing. Jian Wang: Writing – original
draft.
Conclusion: With the development of bioinformatics and sequencing technologies, more discoveries have been done on the crucial roles of non-coding
RNA (ncRNAs) in cellular biology. piRNAs and tRFS as a novel members
of small non-coding RNAs and PIWI proteins found to play different
regulatory functions and new strategies have focused on their therapeutics roles in cancer because of their role in the development of
human cancers in a tissue-specific manner in both tissue and blood
emerging as a highly promising biomarker in different cancers including
CRC. However, research on their function and biosynthesis is not fully
explored yet and needs more investigation for its potential therapeutic
applications and further studies have to be done to uncover sncRNAs
roles as important regulators in CRC in development.
Keywords: piRNA
tRFs
PIWI
Colorectal cancer
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