Competing Endogenous RNA of Snail and Zeb1 UTR in Therapeutic Resistance of Colorectal Cancer

Area of Science:

• Molecular Biology
• Cancer Biology
• Genetics

Background:

• The epithelial-mesenchymal transition (EMT) is crucial for cancer progression and therapeutic resistance.
• Protein abundance of EMT-inducers like Snail and Zeb1 is well-studied, but interactions via untranslated regions (UTRs) in competing endogenous RNA (ceRNA) networks are less understood.

Purpose of the Study:

• To investigate the role of ceRNA networks in regulating EMT-inducers Snail and Zeb1 in colorectal cancer (CRC).
• To explore the functional impact of these ceRNA networks on EMT phenotype and therapeutic resistance in colon cancer.

Main Methods:

• Analysis of synchronized transcript abundance of Snail and Zeb1.
• Identification of a trans-regulatory ceRNA network involving UTRs of EMT inducers and tumor suppressive miRNAs (miR-34, miR-200).
• Examination of The Cancer Genome Atlas (TCGA) samples for genome-wide ceRNA gene sets regulated by miR-34a and miR-200.

Main Results:

• A non-coding RNA network synchronizes Snail and Zeb1 transcript abundance in colorectal cancer.
• A trans-regulatory ceRNA network mediated by miR-34 and miR-200 competition within EMT inducer UTRs was identified.
• This ceRNA network was found to be functional in the EMT phenotype and therapeutic resistance of colon cancer.
• Genome-wide ceRNA gene sets regulated by miR-34a and miR-200 were observed in TCGA colorectal cancer samples.

Conclusions:

• ceRNA networks involving reciprocal interactions between EMT gene UTRs and tumor suppressive microRNAs are functional in colorectal cancer progression.
• These networks play a significant role in the therapeutic resistance of colorectal cancer cells.
• Understanding these ceRNA networks offers potential therapeutic targets for colorectal cancer.