To search for tumor-associated mutations that could affect processing and expression of mature miRNAs, a panel of 91 cancer-derived cell lines was analyzed for sequence variations in 15 miRNAs implicated in tumorigenesis by virtue of their known target transcripts (let-7 family targeting oncogenic Ras) or their localization to sites of frequent chromosomal instability (miR-143, miR-145, miR-26a-1, and miR-21).
MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in tumorigenesis. miR-145 is reported to be down-regulated in several cancers, but knowledge of its targets in colon cancer remains limited.
The loss of miR-145 can result in the activation of factors that promote oncogenesis and cellular pluripotency which in turn could lead to the development of ovarian cancer.
Here, we describe recurrent underexpression of miR-145 in hepatocellular carcinoma (HCC) and the identification of a biological pathway by which miR-145 exerts its functional effects in liver tumorigenesis.
Finally, the in vivo delivery of PU-PEI-miR145 alone significantly suppressed tumorigenesis with stemness, and synergistically improved the survival rate when used in combination with radiotherapy and temozolomide in orthotopic GBM-CD133(+)-transplanted immunocompromised mice.
miR-145 is under-expressed in low-grade, non-invasive and high-grade invasive urothelial bladder carcinoma and may play an important role in the carcinogenesis pathway, being an interesting candidate diagnostic marker.
In this study, we show that miR-145 is significantly downregulated in glioma cell lines compared to normal brain tissue and negatively regulates tumorigenesis.
Since PPAR family members are able to modulate complex miRNAs networks, we hypothesized a role of miRNA-145 in the interaction between PPARγ and SOX9 in colorectal carcinogenesis.
HBV infection promotes cell growth, at least partially, through the HBX-induced downregulation of miRNA-145 expression, which is responsible for the oncogenesis of HBV-associated HCC.
Based on these results, we propose that miR-145 might carry crucial roles in LSCC tumorigenesis, prognosis, metastasis, chemoresistance, and recurrence through regulating stem cell properties of tumor cells.
In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA-RNA crosstalk, which mechanistically modulates several signaling pathways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis.
The receiver-operating characteristic (ROC) curves were used to explore the potential value of miR-143 and miR-145 as biomarkers for predicting HBV-associated HCC tumorigenesis.