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Global Translational Medicine Small RNA therapy for pancreatic cancer

Table 2. List of potential mRNA targets for small RNA drug development against PC
Number Group Target name Effects of this target in Potential application of this target in PC Current stage in small
PC development treatment RNA drug development
1 Group 1: Inhibiting KRAS Promote invasiveness Downregulates KRAS expression to inhibit Clinical research
tumor invasiveness and liver metastasis in invasiveness and metastasis
2 and metastasis TP53 PC Upregulates TP53 expression to inhibit
invasiveness and metastasis
3 STAT3 Downregulates STAT3 expression to inhibit
invasiveness and metastasis
4 EGFR Downregulates EGFR expression to inhibit
invasiveness and metastasis
5 RRM2 Downregulates RRM2 expression to inhibit
invasiveness and metastasis
6 RREB1 Downregulates RREB1 expression to inhibit Pre-clinical research
invasiveness and metastasis
7 CDKN2A Downregulates CDKN2A expression to inhibit
invasiveness and metastasis
8 SMAD4 Downregulates SMAD4 expression to inhibit
invasiveness and metastasis
9 RNF43 Downregulates RNF43 expression to inhibit
invasiveness and metastasis
10 FBXW7 Downregulates FBXW7 expression to inhibit
invasiveness and metastasis
11 MMP2 Downregulates MMP2 expression to inhibit
liver metastasis
12 NF-κB Downregulates NF-κB expression to inhibit
invasiveness and metastasis
13 USP15 Downregulates USP15 expression to inhibit
invasiveness and metastasis
14 Group 2: Enhancing hENT1 Mediate intracellular Upregulates hENT1 expression to enhance Pre-clinical research
sensitivity of PC cells transport of gemcitabine sensitivity of PC patients to gemcitabine
15 to chemotherapy MRP Mediate efflux of a series Downregulates MRP expression to enhance
drugs of chemotherapy drugs sensitivity of PC patients to gemcitabine
such as gemcitabine
16 DPD Breaks down 5-FU into Downregulates DPD expression to enhance
dihydrofluorouracil sensitivity of PC patients to 5-FU
17 Group 3: Improving P4HA1 Leads to accumulation Downregulates P4HA1 expression to decrease Pre-clinical research
the tumor of collagen fibers collagen fiber accumulation
microenvironment in the tumor
microenvironment
Abbreviations: PC: Pancreatic cancer; KRAS: Kirsten rat sarcoma viral oncogene homolog; TP53: Tumor protein p53; STAT3: Signal transducer and
activator of transcription-3; EGFR: Epidermal growth factor receptor; RRM2: Ribonucleotide reductase regulatory subunit M2; RREB1: Ras-responsive
element-binding protein 1; CDKN2A: Cyclin-dependent kinase inhibitor 2A; SMAD4: SMAD family member 4; RNF43: Ring finger protein 43;
FBXW7: F-box and WD repeat domain containing 7; MMP2: Matrix metallopeptidase 2; NF-κB: Nuclear factor kappa-light-chain-enhancer of
activated B cells; USP15: Ubiquitin-specific peptidase 15; hENT1: Human equilibrative nucleoside transporter 1; MRP: Multidrug resistance-associated
protein; DPD: Dihydropyrimidine dehydrogenase; P4HA1: Prolyl 4-hydroxylase subunit alpha 1; 5-FU: 5-fluorouracil.
transporters (hENTs). Previous studies have shown that or decreased activity may contribute to gemcitabine
high expression of hENT1 is linked to improved overall resistance. In addition, multidrug resistance protein
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survival and disease-free survival in PC patients. The (MRP) is a type of ATP-binding cassette transporters
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expression level of hENT1 may serve as a prognostic marker that mediate the efflux of various chemotherapy drugs,
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for PC patients undergoing gemcitabine chemotherapy. such as gemcitabine, thus reducing intracellular drug
Therefore, hENT1 activity is an important determinant of concentration and promoting drug resistance. In
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cancer cell susceptibility to gemcitabine, and its deficiency pancreatic ductal adenocarcinoma (PDAC), MRP1 and
Volume 4 Issue 2 (2025) 15 doi: 10.36922/gtm.8247