Convergence of miR-143 overexpression, oxidative stress and cell death in HCT116 human colon cancer cells.
Sofia E GomesDiane M PereiraCatarina Roma-RodriguesAlexandra R FernandesPedro M BorralhoCecília Maria Pereira RodriguesPublished in: PloS one (2018)
MicroRNAs (miRNAs) regulate a wide variety of biological processes, including tumourigenesis. Altered miRNA expression is associated with deregulation of signalling pathways, which in turn cause abnormal cell growth and de-differentiation, contributing to cancer. miR-143 and miR-145 are anti-tumourigenic and influence the sensitivity of tumour cells to chemotherapy and targeted therapy. Comparative proteomic analysis was performed in HCT116 human colon cancer cells stably transduced with miR-143 or miR-145. Immunoblotting analysis validated the proteomic data in stable and transient miRNA overexpression conditions in human colon cancer cells. We show that approximately 100 proteins are differentially expressed in HCT116 human colon cancer cells stably transduced with miR-143 or miR-145 compared to Empty control cells. Further, Gene Ontology and pathway enrichment analysis indicated that proteins involved in specific cell signalling pathways such as cell death, response to oxidative stress, and protein folding might be modulated by these miRNAs. In particular, antioxidant enzyme superoxide dismutase 1 (SOD1) was downregulated by stable expression of either miR-143 or miR-145. Further, SOD1 gain-of-function experiments rescued cells from miR-143-induced oxidative stress. Moreover, miR-143 overexpression increased oxaliplatin-induced apoptosis associated with reactive oxygen species generation, which was abrogated by genetic and pharmacological inhibition of oxidative stress. Overall, miR-143 might circumvent resistance of colon cancer cells to oxaliplatin via increased oxidative stress in HCT116 human colon cancer cells.
Keyphrases
- cell proliferation
- long non coding rna
- induced apoptosis
- oxidative stress
- long noncoding rna
- cell death
- poor prognosis
- cell cycle arrest
- endoplasmic reticulum stress
- dna damage
- gene expression
- induced pluripotent stem cells
- squamous cell carcinoma
- pi k akt
- dna methylation
- genome wide
- machine learning
- nitric oxide
- big data
- deep learning
- lymph node metastasis