miR-191 expression is frequently altered in several neoplasias, being
upregulated in some, such as pancreatic, colon, lung and prostate carinomas,
and downregulated in others, such as severe medulloblastomas and melanomas.
I have investigated the expression of miR-191 in thyroid neoplasias.
In my thesis I report that miR-191 is downregulated in follicular adenomas and
carcinomas, with a reduction that is almost 2-fold higher in follicular
carcinomas with respect to adenomas. Conversely it is upregulated in thyroid
carcinomas of the papillary histotype (PTCs), in comparison with the normal
thyroid tissue. Consistent with a putative tumour suppressor role of miR-191 in
the development of thyroid neoplasias of the follicular histotype, functional
studies showed that restoration of miR-191 expression in a follicular thyroid
cancer cell line reduces cell growth and migration rate. Furthermore, I found
that miR-191 negatively regulates the expression of CDK6 protein, involved in
cell cycle control, without changing the CDK6 mRNA level and decreases the
activity of a luciferase reporter construct containing the CDK6-3'untranslated
region. These results demonstrate that miR-191 regulates CDK6 at the posttranscriptional
level, resulting in inhibition of cell proliferation and migration
of the follicular thyroid carcinoma cell line; I will show that restoration of
miR-191 expression reduces cell proliferation leading to an increased number
of the cells in the G1 phase of the cell cycle. Finally, in follicular adenomas
and carcinomas, we immunohistochemically detected CDK6 over-expression,
suggesting that miR-191 may have a pathogenic role in thyroid cancer by
controlling CDK6 expression
