Investigating the role of long non-coding RNAs in cisplatin resistance in ovarian cancer — University of Technology
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Investigating the role of long non-coding RNAs in cisplatin resistance in ovarian cancer (14274)

Jaynish S Shah 1 2 , Alexander J Cole 1 2 , Kristie Dickson 1 , Patsy Soon 3 4 , Deborah J Marsh 1 2
  1. Kolling Institute of Medical Research, St Leonards, NSW, Australia
  2. University of Sydney, Sydney, NSW, Australia
  3. Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
  4. University of New South Wales, Sydney, NSW, Australia

Background:

Ovarian cancer is the most lethal gynaecological malignancy and the sixth most common cause of cancer-related death in Australian women. Approximately 80% of patients with ovarian cancer who respond initially to therapy with platin-based drugs develop chemoresistance within two years. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts greater than 200 nucleotides with roles in key cellular processes such as transcription.

Aim:

To determine whether lncRNAs have a role in chemoresistance in ovarian cancer.

Methods:

Cisplatin-sensitive ovarian cancer cell line models A2780 and PEO1 and their cisplatin-resistant counterparts, A2780cisR and PEO4, were profiled using the Human LncProfiler qPCR Array (System Biosciences). Each cell line was profiled in three biological replicates with one qPCR/lncRNA/sample. Expression of each lncRNA was normalised to GAPDH using the ΔΔCt method in ExpressionSuite software (Life Technologies). Comparison of lncRNA profiles of the cisplatin-sensitive cell lines with the drug resistant cell lines identified putative lncRNAs responsible for chemoresistance. Candidate lncRNAs were selected for independent validation using Taqman assays (Life Technologies).

Results:

Of the 90 lncRNAs profiled, 15 had the same expression pattern in both cell line pairs, were expressed at reproducibly detectable levels (Ct ≤ 35) and had single peak melt curves. Urothelial cancer associated 1 (UCA1) was confirmed to be three-fold upregulated (P < 0.001; Taqman assay) in PEO4 compared to  PEO1.

Discussion

Elevated levels of UCA1 have been reported in a number of malignancies, including melanoma, bladder cancer and squamous cell carcinoma of the tongue. It has been linked to metastatic progression in some tumour types. In bladder cancer, UCA1 has been shown to regulate the cell cycle through the phosphoinositide-3-kinase (PI3K) – AKT pathway and promote cisplatin resistance by inducing Wnt signalling. Our results suggest that UCA1 may play a role in chemoresistance in ovarian cancer. 

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