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Global Translational Medicine Small RNA therapy for pancreatic cancer

Table 3. List of potential miRNA targets for small RNA drug development in current PC research
Number Group Target name Roles of miRNAs in pancreatic cancer Type of drug to be
developed
1 Group 1: miRNAs miR-200 family Reverse EMT and inhibits the invasion and metastasis of PC miR-200 mimics
2 expressed at a miR-34 Restores the tumor-suppressive function of p53 in p53-deficient miR-34 mimics
suppressed level human PC cells
in PC
3 miR-143/miR-145 Downregulate KRAS, RREB1, and MAPK signaling genes and inhibit miR-143/miR-145
PC progression mimics
4 miR-146a Downregulates NF-κB expression and inhibits PC progression miR-146a mimics
5 miR-20a/miR-130b Downregulate STAT3 expression and inhibit PC progression miR-20a/miR-130b
mimics
6 miR-29c Inhibits PC cell metastasis and invasion by downregulating MMP2 miR-29c mimics
7 miR-497 Inhibits the proliferation of gemcitabine-resistant PC cells miR-497 mimics
8 miR-137 Inhibits the proliferation and invasion of cancer cells by targeting miR-137 mimics
multiple oncogenes
9 Group 2: miRNAs miR-181 Contributes to chemoresistance in PC by inactivating the Hippo miR-181 inhibitor
with abnormally signaling pathway
10 elevated miR-21 Promotes cancer to evade host immune surveillance and accelerates miR-21 inhibitor
expression in PC PC progression
11 miR-214 Accelerates the proliferation and differentiation of PC cells miR-214 inhibitor
12 miR-155 Promotes the growth and metastasis of PC cells by inhibiting SHIP1 miR-155 inhibitor
13 miR-221/222 Accelerate PC progression through the regulation of matrix miR-221/222 inhibitor
metalloproteinases
14 miR-29a Promotes PC growth by inhibiting tristetraprolin miR-29a inhibitor
15 miR-210 Mediates the occurrence of EMT in PC cells induced by HIF-1α miR-210 inhibitor
under hypoxia
Abbreviations: PC: Pancreatic cancer; miR: miRNA; EMT: Epithelial-mesenchymal transition; KRAS: Kirsten rat sarcoma viral oncogene homolog;
RREB1: Ras-responsive element-binding protein 1; MAPK: Mitogen-activated protein kinase; NF-κB: Nuclear factor kappa-light-chain-enhancer
of activated B cells; STAT3: Signal transducer and activator of transcription-3; MMP2: Matrix metallopeptidase 2; SHIP1: Src homology 2
domain-containing inositol-5-phosphatase 1; HIF-1α: Hypoxia-inducible factor 1-alpha.

and miR-210. All these miRNAs can be targeted by 4. Small RNA drugs
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miRNA inhibitors.
4.1. Mechanisms of action of small RNA drugs
Finally, a search of the Web of Science database using
the keywords “Pancreatic cancer” and “miRNA” identified Small RNA is a class of non-coding RNAs typically ranging
a total of 1,726 articles, which were analyzed for annual from 20 to 30 nucleotides in length. Current research
publication volume (Figure 1). The bibliometric analysis and development on small RNA drugs have focused on
found that, in recent years, the number of published four types, including miRNA mimics, siRNA, antisense
research papers on RNA drugs has been increasing oligonucleotides (ASOs), and aptamers.
(Figure 1). Numerous studies on the transcriptional Previous studies have shown that miRNAs regulate
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level of PC have shown that the dual regulatory a substantial portion of the human transcriptome. The
network of miRNA and transcription factors plays an intricate nature of miRNA regulation is highlighted by the
important role in the formation and progression of PC. ability of a single miRNA to target hundreds of distinct
Therefore, investigating the relationship and interaction mRNAs, whereas multiple miRNAs can also coordinate the
mechanisms between miRNA and traditional treatment regulation of the same mRNA. The classical mechanism
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of PC may provide new insights for the development of by which miRNAs exert their effects involves binding to
small RNA drugs. Finally, interactions between miRNAs the 3’ untranslated region (UTR) of target mRNAs, leading
could represent another emerging field for further to either their degradation or the inhibition of their
exploration. translation (Figure 2A). This process requires miRNA
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Volume 4 Issue 2 (2025) 17 doi: 10.36922/gtm.8247