Small Regulatory Molecules Acting Big in Cancer: Potential Role of Mito-miRs in Cancer

Sharma, Praveen; Bharat,; Dogra, Neeti; Singh, Sandeep

doi:10.2174/1566524019666190723165357

Cited by 12 publications

(10 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7,23 However, it should be noted that the mitochondria is not an autonomous organelle but rather communicates with the nucleus through retrograde signaling. 24,25 This suggests that other small molecules involved in the crosstalk between the nucleus and mitochondria may also play a role in the deregulation of mitochondrial miRNA levels. 24 Thus, the mechanisms underpinning mitochondrial miRNA deregulation in response to I/R injury appear to be complex, warranting further investigation.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: miR-146a inhibits mitochondrial dysfunction and myocardial infarction by targeting cyclophilin D

Cai

et al. 2021

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Increasing evidence suggests that mitochondrial microRNAs (miRNAs) are implicated in the pathogenesis of cardiovascular diseases; however, their roles in ischemic heart disease remain unclear. Herein, we demonstrate that miR-146a is enriched in the mitochondrial fraction of cardiomyocytes, and its level significantly decreases after ischemic reperfusion (I/ R) challenge. Cardiomyocyte-specific knockout of miR-146a aggravated myocardial infarction, apoptosis, and cardiac dysfunction induced by the I/R injury. Overexpression of miR-146a suppressed anoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibiting the mitochondria-dependent apoptotic pathway and increasing the Bcl-2/Bax ratio. miR-146a overexpression also blocked mitochondrial permeability transition pore opening and attenuated the loss of mitochondrial membrane potential and cytochrome c leakage; meanwhile, miR-146a knockdown elicited the opposite effects. Additionally, miR-146a overexpression decreased cyclophilin D protein, not mRNA, expression. The luciferase reporter assay revealed that miR-146a binds to the coding sequence of the cyclophilin D gene. Restoration of cyclophilin D reversed the inhibitory action of miR-146a on cardiomyocyte apoptosis. Furthermore, cardiomyocyte-specific cyclophilin D deletion completely abolished the exacerbation of myocardial infarction and apoptosis observed in miR-146a cardiomyocyte-deficient mice. Collectively, these findings demonstrate that nuclear miR-146a translocates into the mitochondria and regulates mitochondrial function and cardiomyocyte apoptosis. Our study unveils a novel role for miR-146a in ischemic heart disease.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED: miR-146a inhibits mitochondrial dysfunction and myocardial infarction by targeting cyclophilin D

Cai

et al. 2021

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…miRNAs are encoded in the nuclear genome and exported to the cytosol where they perform most of their functions, however, the expression of miRNAs within the mitochondrion has been recently demonstrated, which can be either mitochondrial encoded or transcribed within the nucleus and subsequently localized to mitochondria, this miRNAs are termed as mitomiRs (89). MitomiRs are likely to contribute to some post-transcriptional regulation of gene expression related to the mitochondrial functions (90).…”

Section: Mtorc1 and Mitochondrial Regulation By Mirnas In Cancermentioning

confidence: 99%

mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

et al. 2019

View full text Add to dashboard Cite

Continuous proliferation of tumor cells requires constant adaptations of energy metabolism to rapidly fuel cell growth and division. This energetic adaptation often comprises deregulated glucose uptake and lactate production in the presence of oxygen, a process known as the "Warburg effect." For many years it was thought that the Warburg effect was a result of mitochondrial damage, however, unlike this proposal tumor cell mitochondria maintain their functionality, and is essential for integrating a variety of signals and adapting the metabolic activity of the tumor cell. The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of numerous cellular processes implicated in proliferation, metabolism, and cell growth. mTORC1 controls cellular metabolism mainly by regulating the translation and transcription of metabolic genes, such as peroxisome proliferator activated receptor γ coactivator-1 α (PGC-1α), sterol regulatory element-binding protein 1/2 (SREBP1/2), and hypoxia inducible factor-1 α (HIF-1α). Interestingly it has been shown that mTORC1 regulates mitochondrial metabolism, thus representing an important regulator in mitochondrial function. Here we present an overview on the role of mTORC1 in the regulation of mitochondrial functions in cancer, considering new evidences showing that mTORC1 regulates the translation of nucleus-encoded mitochondrial mRNAs that result in an increased ATP mitochondrial production. Moreover, we discuss the relationship between mTORC1 and glutaminolysis, as well as mitochondrial metabolites. In addition, mitochondrial fission processes regulated by mTORC1 and its impact on cancer are discussed. Finally, we also review the therapeutic efficacy of mTORC1 inhibitors in cancer treatments, considering its use in combination with other drugs, with particular focus on cellular metabolism inhibitors, that could help improve their anti neoplastic effect and eliminate cancer cells in patients. de la Cruz López et al. mTORC1 and Mitochondrial Functions Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The handling editor declared a shared affiliation, though no other collaboration, with with several of the authors AG and KC.

show abstract

“…Both code for subunits 3 and 4 of mitochondrial encoded NADH dehydrogenase, respectively, and are part of CI. 31,32 CI is the largest enzyme complex that binds to the NADH substrate and initiates the first step in the electron transport process, which leads to energy production in the form of ATP. Their upregulation indicates increased CI activity and results in higher ATP production.…”

Section: Dca Induces Expression Of Tumor Suppressor Mirnasmentioning

confidence: 99%

Combinatorial Effect of DCA and Let-7a on Triple-Negative MDA-MB-231 Cells: A Metabolic Approach of Treatment

Sharma

Singh

2020

Integr Cancer Ther

Self Cite

View full text Add to dashboard Cite

Dichloroacetate (DCA) is a metabolic modulator that inhibits pyruvate dehydrogenase activity and promotes the influx of pyruvate into the tricarboxylic acid cycle for complete oxidation of glucose. DCA stimulates oxidative phosphorylation (OXPHOS) more than glycolysis by altering the morphology of the mitochondria and supports mitochondrial apoptosis. As a consequence, DCA induces apoptosis in cancer cells and inhibits the proliferation of cancer cells. Recently, the role of miRNAs has been reported in regulating gene expression at the transcriptional level and also in reprogramming energy metabolism. In this article, we indicate that DCA treatment leads to the upregulation of let-7a expression, but DCA-induced cancer cell death is independent of let-7a. We observed that the combined effect of DCA and let-7a induces apoptosis, reduces reactive oxygen species generation and autophagy, and stimulates mitochondrial biogenesis. This was later accompanied by stimulation of OXPHOS in combined treatment and was thus involved in metabolic reprogramming of MDA-MB-231 cells.

show abstract

Small Regulatory Molecules Acting Big in Cancer: Potential Role of Mito-miRs in Cancer

Cited by 12 publications

References 94 publications

RETRACTED: miR-146a inhibits mitochondrial dysfunction and myocardial infarction by targeting cyclophilin D

RETRACTED: miR-146a inhibits mitochondrial dysfunction and myocardial infarction by targeting cyclophilin D

mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

Combinatorial Effect of DCA and Let-7a on Triple-Negative MDA-MB-231 Cells: A Metabolic Approach of Treatment

Contact Info

Product

Resources

About