Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells.
Andrea SantosIon CristóbalCristina CaramésMelani LuqueMarta Sanz-ÁlvarezJuan Madoz-GúrpideFederico RojoJesús García-FoncillasPublished in: International journal of molecular sciences (2023)
MicroRNA (miR)-19b is deregulated in colorectal cancer (CRC) and locally advanced rectal cancer (LARC), predicting worse outcome and disease progression in CRC patients, and acting as a promising prognostic marker of patient recurrence and pathological response to 5-fluorouracil (5-FU)-based neoadjuvant chemoradiotherapy in LARC. Moreover, there is a strong inverse correlation between miR-19b and PPP2R5E in LARC, and both predict the response to neoadjuvant therapy in LARC patients. However, the functional role of the miR-19b/PPP2R5E axis in CRC cells remains to be experimentally evaluated. Here, we confirm with luciferase assays that miR-19b is a direct negative regulator of PPP2R5E in CRC, which is concordant with the observed decreased PP2A activity levels after miR-19b overexpression. Furthermore, PPP2R5E downregulation plays a key role mediating miR-19b-induced oncogenic effects, increasing cell viability, colonosphere formation ability, and the migration of CRC cells. Lastly, we also confirm the role of miR-19b mediating 5-FU sensitivity of CRC cells through negative PPP2R5E regulation. Altogether, our findings demonstrate the functional relevance of the miR-19b/PPP2R5E signaling pathway in disease progression, and its potential therapeutic value determining the 5-FU response of CRC cells.
Keyphrases
- rectal cancer
- locally advanced
- induced apoptosis
- signaling pathway
- end stage renal disease
- cell cycle arrest
- chronic kidney disease
- endoplasmic reticulum stress
- squamous cell carcinoma
- newly diagnosed
- neoadjuvant chemotherapy
- radiation therapy
- cell death
- stem cells
- pi k akt
- epithelial mesenchymal transition
- lymph node
- cell proliferation
- phase ii study
- bone marrow
- smoking cessation