AI Article Synopsis
- - The study investigates the role of microRNA-320 (miRNA-320) in the progression of colitis-associated colorectal cancer (CAC), finding that its downregulation is linked to increased tumor formation in mice with inflammatory bowel disease (IBD).
- - Administration of miRNA-320 through a lentiviral vector improved colonic inflammation and significantly reduced tumor numbers, indicating its potential as a therapeutic target against CAC.
- - Mechanistically, miRNA-320 was shown to inhibit cancer cell proliferation, migration, and invasion while downregulating key proteins involved in tumor progression, such as BCL-xl and the IL-6 signaling pathway.
Article Abstract
Background: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD). microRNA-320 (miRNA-320) promotes intestinal mucosal barrier repair in IBD and inhibits tumor progression. However, the role of miRNA-320 in the progression of CAC remains to be defined. We studied the mechanisms of miRNA-320 in the progression of CAC in mice.
Methods: CAC was induced in mice (C57BL/B6) by the administration of azoxymethane (AOM) and dextran sulfate sodium (DSS), and the mice were given a lentiviral vector (LV) overexpressing mmu-miRNA-320. The level of miRNA-320 was analyzed by quantitative real-time polymerase chain reaction (qPCR). Colonic inflammation, histological analysis, and tumorigenesis were evaluated. Ki-67 in colonic tissues was examined by immunohistochemistry. B-cell lymphoma-extra large (BCL-xl) and proliferating cell nuclear antigen (PCNA) expression was examined by Western blot. Furthermore, the proliferation, migration, and invasion of colorectal cancer (CRC) cells were evaluated. The levels of interleukin-6 receptor (IL-6R), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3) were examined by Western blot and qPCR.
Results: miRNA-320 was downregulated in CAC mice (0.57±0.13 1.00±0.12, =-5.95, P<0.001). miRNA-320 decreased the disease activity index (DAI) scores, improved colonic inflammation, and inhibited tumor formation (tumor number: 8.00±2.90 13.67±2.73, =-3.49, P<0.01) in mice with CAC. miRNA-320 suppressed the expression of BCL-xl, PCNA, and Ki-67 (0.38±0.07 0.69±0.08, =-7.30, P<0.001). miRNA-320 inhibited colon cancer cell proliferation, migration, and invasion. miRNA-320 significantly inhibited the levels of IL-6R [colon tissue messenger RNA (mRNA): 4.06±1.44 10.05±1.55, =-6.94, P<0.001], STAT3, and p-STAT3 and . Silencing IL-6R expression partially reversed the IL-6R/STAT3-suppressing and tumor-inhibiting effect of miRNA-320.
Conclusions: miRNA-320 inhibits tumorigenesis in mice with CAC by suppressing IL-6R/STAT3 expression, and IL-6R is a target gene of miRNA-320.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086045 | PMC |
| http://dx.doi.org/10.21037/jgo-22-237 | DOI Listing |
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