Journal Article

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

Tan, Benedict Jian Wei, Sun, Li Li, Tan, Daniel Shao Weng, Yang, Henry, Soo, Ross Andrew, Lim, Wan Teck, Lim, Priscilla Xin Hui, Lim, Bing, Nga, Min En, Tan, Eng Huat, Malusay, Shanneen Rossellini Y, Lim, Elaine Hsuen, Lunny, Declan Patrick, Tai, Bee Choo, Lee, Jeravan Zili, Zhang, Wen Cai, Shyh-Chang, Ng, Chin, Tan Min, Pang, Yin Huei, Tam, Wai Leong, Lim, Edwin Kok Hao, Leow, Yi Ning

2016

Overview

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. miRNAs can function either as proto-oncogenes or tumour suppressors in several cancers; however their function in tumour initiating cells is unclear. Here, Zhang et al . show that tumour initiating cell-specific miR-1246 and miR-1290 promote lung cancer initiation and metastasis and could serve as prognostic markers.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/100 / 13/106 / 13/109 / 13/31 / 13/89 / 38/39 / 631/337/384/331 / 631/67/1612/1350 / 631/67/1857 / 692/420/755 / 82/80 / A549 Cells / Animals / Antineoplastic Combined Chemotherapy Protocols - pharmacology / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - pathology / Carcinoma, Non-Small-Cell Lung - therapy / Disease Progression / Female / Gene Expression Regulation, Neoplastic / HEK293 Cells / Heterogeneity / Humanities and Social Sciences / Humans / Hydroxychloroquine - pharmacology / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Lung Neoplasms - therapy / Lymphatic Metastasis / Mice / MicroRNAs - antagonists & inhibitors / MicroRNAs - genetics / MicroRNAs - metabolism / multidisciplinary / Neoplastic Stem Cells - metabolism / Neoplastic Stem Cells - pathology / Nucleic acids / Oligonucleotides - administration & dosage / Oligonucleotides - genetics / Oligonucleotides - metabolism / Quinazolines - pharmacology / Science / Science (multidisciplinary) / Signal Transduction / Survival Analysis / Tumor Burden / Tumors / Xenograft Model Antitumor Assays