LINC00857 expression predicts and mediates the response to platinum-based chemotherapy in muscle-invasive bladder cancer.
Aleksandra M DudekJasmijn G M van KampenJ Alfred WitjesLambertus A L M KiemeneyGerald W VerhaeghPublished in: Cancer medicine (2018)
Approximately 20% of patients with bladder cancer are diagnosed with muscle-invasive disease (MIBC). The treatment involves radical cystectomy, but almost 50% of patients with MIBC eventually relapse and develop metastasis. The use of platinum-based chemotherapy in the neoadjuvant setting or for metastatic patients has been shown to improve the overall survival in a subset of patients. Unfortunately, no biomarkers are available to select patients with MIBC who will benefit from chemotherapy or to monitor the efficacy of the treatment. Recently, long noncoding RNAs (lncRNAs) were shown to regulate a variety of processes involved in the development and progression of cancer, including bladder cancer. Moreover, several lncRNAs have been shown to play a role in chemotherapy resistance. Here, we analyzed lncRNA expression associated with response to platinum-based chemotherapy in metastatic MIBC using data from the MiTranscriptome lncRNA expression database. Expression of the lncRNA, LINC00857, was found to be upregulated in tumors from patients that did not respond to platinum-based chemotherapy. Moreover, high expression of LINC00857 is correlated with shorter recurrence-free and overall survival of patients with MIBC. Knockdown of LINC00857 significantly decreased cell viability of bladder cancer cell lines through the induction of apoptosis. Furthermore, LINC00857 knockdown sensitized UM-UC-3 and T24 bladder cancer cells to cisplatin, via the negative regulation of the LMAN1 gene. Our data indicate that LINC00857 plays an important role in the regulation of response to platinum-based chemotherapy. LINC00857 potentially could serve as a novel prognostic and predictive biomarker and might be a therapeutic target to overcome cisplatin resistance in patients with MIBC.
Keyphrases
- long non coding rna
- poor prognosis
- long noncoding rna
- locally advanced
- end stage renal disease
- cell proliferation
- ejection fraction
- newly diagnosed
- chronic kidney disease
- squamous cell carcinoma
- small cell lung cancer
- prognostic factors
- emergency department
- binding protein
- muscle invasive bladder cancer
- lymph node
- spinal cord injury
- free survival
- oxidative stress
- electronic health record
- chemotherapy induced
- signaling pathway
- combination therapy
- genome wide analysis