MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.
Cell Line, Tumor
Drug Resistance, Neoplasm
E2F1 Transcription Factor
Proto-Oncogene Proteins c-akt
MetadataShow full item record
CitationMicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma. 2015, 10 (7):e0134180 PLoS ONE
AbstractOesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC.
- Low miR-187 expression promotes resistance to chemoradiation therapy in vitro and correlates with treatment failure in patients with esophageal adenocarcinoma.
- Authors: Lynam-Lennon N, Bibby BA, Mongan AM, Marignol L, Paxton CN, Geiersbach K, Bronner MP, O'Sullivan J, Reynolds J, Maher SG
- Issue date: 2016 May 23
- Silencing microRNA-330-5p increases MMP1 expression and promotes an invasive phenotype in oesophageal adenocarcinoma.
- Authors: Bibby BAS, Miranda CS, Reynolds JV, Cawthorne CJ, Maher SG
- Issue date: 2019 Aug 7
- MicroRNA-17 is downregulated in esophageal adenocarcinoma cancer stem-like cells and promotes a radioresistant phenotype.
- Authors: Lynam-Lennon N, Heavey S, Sommerville G, Bibby BA, Ffrench B, Quinn J, Gasch C, O'Leary JJ, Gallagher MF, Reynolds JV, Maher SG
- Issue date: 2017 Feb 14
- Circulating serum microRNA-345 correlates with unfavorable pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer.
- Authors: Yu J, Li N, Wang X, Ren H, Wang W, Wang S, Song Y, Liu Y, Li Y, Zhou X, Luo A, Liu Z, Jin J
- Issue date: 2016 Sep 27
- MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.
- Authors: Svoboda M, Sana J, Fabian P, Kocakova I, Gombosova J, Nekvindova J, Radova L, Vyzula R, Slaby O
- Issue date: 2012 Nov 20