Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression

Wen Cai Zhang, Tan Min Chin, Henry Yang, Min En Nga, Declan Patrick Lunny, Edwin Kok Hao Lim, Li Li Sun, Yin Huei Pang, Yi Ning Leow, Shanneen Rossellini Y Malusay, Priscilla Xin Hui Lim, Jeravan Zili Lee, Benedict Jian Wei Tan, Ng Shyh-Chang, Elaine Hsuen Lim, Wan Teck Lim, Daniel Shao Weng Tan, Eng Huat Tan, Bee Choo Tai, Ross Andrew Soo, Wai Leong Tam () and Bing Lim ()
Additional contact information
Wen Cai Zhang: Genome Institute of Singapore
Tan Min Chin: Cancer Science Institute of Singapore, National University of Singapore
Henry Yang: Cancer Science Institute of Singapore, National University of Singapore
Min En Nga: National University Hospital
Declan Patrick Lunny: Institute of Medical Biology
Edwin Kok Hao Lim: Genome Institute of Singapore
Li Li Sun: Genome Institute of Singapore
Yin Huei Pang: National University Hospital
Yi Ning Leow: Genome Institute of Singapore
Shanneen Rossellini Y Malusay: Genome Institute of Singapore
Priscilla Xin Hui Lim: Genome Institute of Singapore
Jeravan Zili Lee: Genome Institute of Singapore
Benedict Jian Wei Tan: Genome Institute of Singapore
Ng Shyh-Chang: Genome Institute of Singapore
Elaine Hsuen Lim: Tan Tock Seng Hospital
Wan Teck Lim: National Cancer Centre Singapore
Daniel Shao Weng Tan: Genome Institute of Singapore
Eng Huat Tan: National Cancer Centre Singapore
Bee Choo Tai: Saw Swee Hock School of Public Health, National University of Singapore
Ross Andrew Soo: Cancer Science Institute of Singapore, National University of Singapore
Wai Leong Tam: Genome Institute of Singapore
Bing Lim: Genome Institute of Singapore

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: Abstract The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets.

Date: 2016
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DOI: 10.1038/ncomms11702

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