Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3

Wing Pui Tsang, Tim Tak Kwok
Apoptosis: An International Journal on Programmed Cell Death 2008, 13 (10): 1215-22
MicroRNAs (miRNA) are endogenously expressed non-coding RNAs that regulate gene expression post-transcriptionally. Let-7a miRNA is a founding member in the let-7 family and its down-regulation in association with over-expression of RAS and HMGA2 oncogenes has previously been reported. In the present study, caspase-3, the executioner caspase, was confirmed to be the target of let-7a as ectopic expression of let-7a decreased the luciferase activity of a reporter construct containing the 3' untranslated region of caspase-3 and at the same time repressed the enzyme expression in human squamous carcinoma A431 cells and hepatocellular carcinoma HepG2 cells. Moreover, let-7a was over-expressed while caspase-3 was down-regulated in A10A cells, a doxorubicin-resistant A431 subline. Enforced let-7a expression increased the resistance in A431 cells and HepG2 cells to apoptosis induced by therapeutic drugs such as interferon-gamma, doxorubicin and paclitaxel. On the other hand, down-regulation of let-7a by the anti-let-7a inhibitor increased the doxorubicin-induced apoptosis in A431 parent cells, A10A cells and HepG2 cells while the increase was suppressed by caspase-3 inhibitor. Both anti-let-7a inhibitor and caspase-3 inhibitor however failed to affect the drug-induced apoptosis in human breast cancer MCF7 cells, the cells that do not express caspase-3. Therefore, let-7a by targeting caspase-3 may play a functional role in modulating drug-induced cell death in human cancer cells.

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"