miR-1 induces growth arrest and apoptosis in malignant mesothelioma

Yue Xu, Ming Zheng, Robert E Merritt, Joseph B Shrager, Heather A Wakelee, Robert A Kratzke, Chuong D Hoang
Chest 2013, 144 (5): 1632-1643

BACKGROUND: We investigated microRNA expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel microRNA that are potentially involved in the oncogenic transformation of human pleural cells.

METHODS: microRNA microarray transcriptional profiling studies of 25 MPM primary tumors were performed. We used normal pleural tissue from an unmatched patient cohort as normal comparators. To confirm microarray data, we used real-time quantitative polymerase chain reaction. Representative cell lines H513 and H2052 were used in functional analyses of miR-1.

RESULTS: In addition to several novel MPM-associated microRNAs, we observed that the expression level of miR-1 was significantly lower in tumors as compared with normal pleural specimens. Subsequently, pre-miR of miR-1 was introduced into MPM cell lines to overexpress this microRNA. Phenotypic changes of these altered cells were assayed. The cellular proliferation rate was significantly inhibited after overexpression of miR-1. Early and late apoptosis was increased markedly in miR-1-transfected cell lines. Taken together, these data suggested that overexpression of miR-1 induced apoptosis in these MPM cell lines, acting as a tumor suppressor. We confirmed our observations by assessing in the transduced MPM cells cell cycle-related, proapoptotic, and antiapoptotic genes, which all showed coordinated, significant changes characteristic of the apoptotic phenotype.

CONCLUSIONS: Further investigation and validation of our microRNA database of MPM may elucidate previously unrecognized molecular pathways and/or mechanisms by identifying novel microRNAs that are involved in malignant transformation. Our study has now found miR-1 to be one of these MPM-associated microRNAs, with potential pathogenic and therapeutic significance.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"