RGD Reference Report - miR-193a-5p as a promising therapeutic candidate in colorectal cancer by reducing 5-FU and Oxaliplatin chemoresistance by targeting CXCR4. - Rat Genome Database

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miR-193a-5p as a promising therapeutic candidate in colorectal cancer by reducing 5-FU and Oxaliplatin chemoresistance by targeting CXCR4.

Authors: Azar, Mohammad Reza Mohammad Hoseini  Aghazadeh, Hamed  Mohammed, Halgurd Nadhim  Sara, Mehdi Rezai Seghin  Hosseini, Arezoo  Shomali, Navid  Tamjidifar, Rozita  Tarzi, Saeed  Mansouri, Mahmoud  Sarand, Sahar Pashaei  Marofi, Faroogh  Akbari, Morteza  Xu, Huaxi  Shotorbani, Siamak Sandoghchian 
Citation: Azar MRMH, etal., Int Immunopharmacol. 2021 Mar;92:107355. doi: 10.1016/j.intimp.2020.107355. Epub 2021 Jan 8.
RGD ID: 151665332
Pubmed: PMID:33429333   (View Abstract at PubMed)
DOI: DOI:10.1016/j.intimp.2020.107355   (Journal Full-text)

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide. The role of microRNAs (miRNAs/miRs) as small (19-25 nucleotides in length) non-coding RNA molecules that modify gene expression has been shown in several types of cancer. 5-Fluorouracil (5-FU) and oxaliplatin (Ox) are two common chemotherapeutic agents used to treat cancer. The present study aimed to evaluate the expression levels of miR-193a-5p in CRC, and its effect on the C-X-C Motif Chemokine Receptor 4 (CXCR4) target gene alone and in combination with chemotherapeutic drugs, to determine its possible role in chemoresistance. CRC tissues and adjacent non-cancerous tissue were obtained from 67 patients who had undergone surgery to determine the expression levels of miR-193a-5p and CXCR4. Subsequently, qPCR and Western blotting were performed to determine the effect of miR-193a-5p and chemotherapy drugs on CXCR4. ŮŽAlso, MTT assay, and flow cytometry was performed to determine their role in cell viability and apoptosis. Besides, the relationship between miR-193a-5p and CXCR4 with patients' clinical features was investigated. The results of the present study showed that miR-193a-5p was significantly downregulated, whereas CXCR4 was significantly upregulated in tumor tissues obtained from patients with CRC compared with the adjacent non-tumor healthy controls. In addition, the upregulation of miR-193-5p reduced the expression levels of CXCR4, particularly in combination with 5-FU and OX. Besides, using rescue experiments, the present study showed that miR-193a-5p replacement was able to suppress CXCR4-induced CRC cell proliferation by directly targeting CXCR4. Furthermore, there was a significant association between miR-193a-5p and CXCR4 with certain clinicopathological characteristics, particularly with metastasis-related features. These results suggest that miR-193a-5p serves a tumor-suppressive function in CRC and can directly target CXCR4 and decrease its mRNA and protein expression levels. Additionally, miR-193a-5p in combination with 5-FU and Ox potentiated reducing CXR4 expression, which may reveal its contribution to tumor chemoresistance. In conclusion, miR-193-5p may be applicable as a prognostic and diagnostic marker, and also serve as a therapeutic factor by reducing CXCR4 in combination with chemotherapeutic drugs.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCR4Humancolorectal cancer disease_progressionIEP mRNA:increased expression:colorectum (human)RGD 
Cxcr4Ratcolorectal cancer disease_progressionISOCXCR4 (Homo sapiens)mRNA:increased expression:colorectum (human)RGD 
Cxcr4Mousecolorectal cancer disease_progressionISOCXCR4 (Homo sapiens)mRNA:increased expression:colorectum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcr4  (C-X-C motif chemokine receptor 4)

Genes (Mus musculus)
Cxcr4  (C-X-C motif chemokine receptor 4)

Genes (Homo sapiens)
CXCR4  (C-X-C motif chemokine receptor 4)


Additional Information