Page 99 - CSIR-IGIB Annual Report 2020-21
P. 99
microRNA(s) as regulator of mitochondrial activity antimiR-128 treatment. Our findings reveal that
/ mitochondrial function inhibition of miR-128 can be a new potential target
Mitochondria are not only important for cellular for reversing the effects of metabolic disorders of
bioenergetics but also lie at the heart of critical skeletal muscle as observed during many
metabolic pathways. They can rapidly adjust pathophysiological conditions such as obesity and
themselves in response to changing conditions type II diabetes.
and the metabolic needs of the cell. Mitochondrial mitomiRs are class of miRNA(s) that regulate
involvement as well as its dysfunction occurs in mitochondrial gene expression and function.
many human pathologies, such as cardiovascular Insilico analysis of predicted targets of mitomiRs
disease, diabetes, cancer, and neurological targeting energy metabolism have identified
diseases. Critical role of miRNA(s) in regulating several significantly altered pathways (needs in
the mitochondrial activity/function in normal and vivo validations) that may provide a new
disease is emerging. In our laboratory we therapeutic approach for the treatment of human
observed that miR-195 modulates mitochondrial diseases. In vitro as well as in vivo validations of
dynamics (a collective term for mitochondrial the same are being currently studied in the
fusion and fission) by targeting MFN2 thereby laboratory.
impairing mitochondrial function. Imaging
experiments upon miR-195 treatment revealed microRNA based therapeutics/diagnostics for
extensive mitochondria fission. We have further cancer and psoriasis
shown that miR-195 enhances mitochondrial SOD- Breast cancer is the most frequent cancer leading
2 expression but does not affect PINK1 levels in to death in women worldwide. The deregulation
breast cancer cells. Our findings suggest a of the miRNA expression network is found to be
therapeutic potential of miR-195 in both ER- associated with cancer development, progression,
positive as well as ER-negative breast cancer cells. and response to therapy. Several studies showed
microRNA(s) as a potential modulator of gene
In many pathological conditions, mitochondrial expression. Our laboratory has unveiled that miR-
morphology is also altered due to impaired 195 binds to the 3'UTR sequence of Bcl2 to down-
mitochondrial dynamics and dysfunction. We regulate its expression and that renders pro-
recently showed that miR-128 reduces apoptotic effects in breast cancer cells. In another
mitochondrial biogenesis by directly targeting study, we have further shown that miR-195
PGC1α. The expression of nuclear respiratory inhibits proliferation, invasion, and breast cancer
factors 1 and 2 (NRF1 and NRF2, respectively), and metastasis. These findings propose hsa-miR-195
mitochondrial transcription factor A (TFAM) were as a potential anticancer molecule with promising
decreased in C2C12 myoblasts upon therapeutic value in breast cancer. In addition to
overexpression of miR-128. Also, miR-128 is its pro-apoptotic role, hsa-miR-195 has also been
shown to promote mitochondrial dysfunction by shown to implicate mitochondrial dynamics that in
directly targeting NADH Dehydrogenase turn diminishes oxygen consumption rate in
(Ubiquinone) Fe-S Protein 4 (NDUFS4). The breast cancer cells. In our recently approved
mitochondrial dynamics and morphology were projects from CSIR we intend to use next
impaired post miR-128 overexpression, as generation sequencing/profiling technologies for
revealed by downregulation of fusion proteins identification of noncoding RNAs and explore their
(mitofusin1 and 2, i.e., MFN1 and MFN2, potential role as biomarkers of chemo resistance
respectively) and upregulation of fission protein in breast cancer and understand their mechanism
(dynamin-related protein 1, i.e., DRP1). of action.
Conversely, inhibition of miR-128 expression
improved mitochondrial biogenesis, function, and Psoriasis is recognized as a T cell mediated
dynamics, as evidenced by increased inflammatory hyper proliferative skin disorder.
mitochondrial mass and ATP production after Despite of availability of various treatments,
Annual Report 2020-21 96
