This invention generally relates to a design and method for developing novel anti-tumor /
cancer drugs, vaccines and therapies, using
microRNA (miRNA) and its shRNA homologues / derivatives. More particularly, the present invention relates to the use of a
nucleic acid composition capable of expressing mir-302-like
gene silencing effectors upon delivery into human cells and then silencing mir-302-targeted
cell cycle regulators and oncogenes, resulting in an
inhibitory effect on tumor /
cancer cell growth and
metastasis. Mir-302 is the most predominant miRNA found in human embryonic stem (hES) and induced pluripotent stem (iPS) cells, yet its function is unclear. The present invention establishes that in humans mir-302 concurrently suppressed both
cyclin-E-CDK2 and
cyclin-D-CDK4 / 6 pathways and eventually blocked over 70% of the G1-S transition. Simultaneously, mir-302 also silences BMI-1, a
cancer stem cell marker, and subsequently promotes the tumor
suppressor functions of p16Ink4a and p14 / p19Arf in inhibiting CDK4 / 6-mediated
cell proliferation. Therefore, the present invention for the first time reveals the tumor
suppressor function of mir-302 in humans. This novel finding advances the design and method for developing new
cancer drugs, vaccines and therapies directed against multiple kinds of human tumors and cancers, in particular including, but not limited, malignant
skin,
prostate, breast and liver cancers as well as various tumors.