RNA Sequencing of Osteosarcoma Gene Expression Profile Revealed that miR-214-3p Facilitates Osteosarcoma Cell Proliferation via Targeting Ubiquinol-Cytochrome c Reductase Core Protein 1 (UQCRC1)

Zhao, Xin; Wang, Qingyu; Lin, Feifei; Wang, Xiaonan; Wang, Yanbing; Wang, Jincheng; Wang, Chenyu

doi:10.12659/msm.917375

Cited by 9 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The abnormal expression of UQCRC1 has been reported in various human cancers. UQCRC1 is upregulated in breast cancer ( 41 ), ovarian cancer ( 41 ), and PC ( 18 ), while downregulated in colorectal cancer ( 16 ), osteosarcoma ( 42 ), and clear cell renal cell carcinoma ( 17 ). To date, the mechanistic studies of UQCRC1 in tumors only focused on the tumor cells themselves.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Mitochondrial UQCRC1 in Pancreatic Cancer Impairs Antitumor Immunity of Natural Killer Cells via Elevating Extracellular ATP

et al. 2022

View full text Add to dashboard Cite

Pancreatic cancer (PC) is one of the most lethal malignancies characterized by a highly immunosuppressive tumor microenvironment (TME). Previously, we have reported that ubiquinol-cytochrome c reductase core protein I (UQCRC1), a key component of mitochondrial complex III, is generally upregulated in PC and produces extracellular ATP (eATP) to promote PC progression. Here, we sought to investigate whether the oncogenic property of UQCRC1 is generated through its effects on natural killer (NK) cells in the TME. We found that UQCRC1 overexpression in PC cells inhibited cytotoxicity of NK cells, as well as the infiltration of NK cells toward PC, whereas knockdown of UQCRC1 enhanced the cytotoxicity and chemotaxis of NK cells. Adoptive NK cell therapy in the subcutaneous mouse model and CIBERSORTx analysis with human PC specimens confirmed UQCRC1 elicited immunosuppressive effects on NK cells. Such UQCRC1-induced impairment of NK cells was mediated by eATP and its metabolite adenosine via P2Y11R and A2AR, respectively. Mechanistically, we found the UQCRC1/eATP axis reduced the expression of chemokine CCL5 in cancer cells and altered the balance of activating receptor DNAM-1 and inhibitory receptor CD96 on NK-92MI cells, resulting in decreased chemotaxis and exhausted phenotype of NK-92MI cells. Taken together, our study provides the evidence to support a novel mechanism by which energy metabolism change in cancer cells remodels the TME and impedes NK cell surveillance. It also suggests that targeting UQCRC1 may be a potential combined strategy for PC immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased Expression of Mitochondrial UQCRC1 in Pancreatic Cancer Impairs Antitumor Immunity of Natural Killer Cells via Elevating Extracellular ATP

et al. 2022

View full text Add to dashboard Cite

show abstract

“…miR-214-3p is one of the miRNAs with oncogene properties that are important in the process of various cancers ( 9 ). The miR-214-3p level is markedly increased in osteosarcoma ( 9 , 10 ). Liver cancer has been shown to have oncogene capabilities.…”

Section: Discussionmentioning

confidence: 99%

Formononetin inhibits osteosarcoma cell proliferation and promotes apoptosis by regulating the miR-214-3p/phosphatase and tensin homolog pathway

Li¹,

Shen²,

Lu³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Phytoestrogens have a similar molecular structure to estrogens which can produce either estrogenic or anti-estrogenic effects. It is generally believed that phytoestrogens combine with the estrogen receptor of osteosarcoma cells, affecting a variety of signal transduction pathways and cell metabolism, resulting in altered cell proliferation, differentiation, apoptosis, invasion and migration ability. Formononetin (FN) is the active ingredient of traditional Chinese medicine astragalus, angelica, and Pueraria lobate. Our study aims to detect the role of FN on MG-63 cell viability and apoptosis through regulating phosphatase and tensin homolog (PTEN) expression via MicroRNA-214-3p (miR-214-3p). Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Caspase 3 assay evaluated cell viability and apoptosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot evaluated the mRNA and protein expressions, respectively. The binding site of miR-214-3p/PTEN was detected via dual luciferase assay. Results: FN suppressed cell viability and induced apoptosis, and decreased miR-214-3p level and promoted PTEN expression. PTEN was then regarded as a target of miR-214-3p, and FN improved PTEN level via inhibiting miR-214-3p. Further analysis showed that overexpressed miR-214-3p improved cell viability and suppressed apoptosis of MG-63 cells by inhibiting PTEN expression. Conclusions: Finally, our results revealed that FN inhibited cell viability and induced apoptosis by regulating miR-214-3p. FN acted as a new treatment for MG-63 cells via increasing PTEN level by inhibiting the miR-214-3p level.

show abstract

“…A later study by the same group confirmed the role of miR-127 and miR-376a in tumour suppression in osteosarcoma cells [ 238 ]. In contrast, osteosarcoma cell proliferation can be enhanced via targeting of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) with miR-214-3p [ 239 ]. In gastric cancer, the miR-370/UQCRC2 axis positively regulates the epithelial-mesenchymal transition (EMT) signalling that affects tumour proliferation and metastasis [ 240 ].…”

Section: Mirna Regulation Of Mitochondrial Genesmentioning

confidence: 99%

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential

Wagner

Kosnáčová

Chovanec

et al. 2022

IJMS

View full text Add to dashboard Cite

Mitochondria are dynamic organelles managing crucial processes of cellular metabolism and bioenergetics. Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increasing evidence suggests that mtDNA mutations, mtDNA epigenetics and miRNA regulations dynamically modify signalling pathways in an altered microenvironment, resulting in cancer initiation and progression and aberrant therapy response. In this review, we discuss mitochondria as organelles importantly involved in tumorigenesis and anti-cancer therapy response. Tumour treatment unresponsiveness still represents a serious drawback in current drug therapies. Therefore, studying aspects related to genetic and epigenetic control of mitochondria can open a new field for understanding cancer therapy response. The urgency of finding new therapeutic regimens with better treatment outcomes underlines the targeting of mitochondria as a suitable candidate with new therapeutic potential. Understanding the role of mitochondria and their regulation in cancer development, progression and treatment is essential for the development of new safe and effective mitochondria-based therapeutic regimens.

show abstract

RNA Sequencing of Osteosarcoma Gene Expression Profile Revealed that miR-214-3p Facilitates Osteosarcoma Cell Proliferation via Targeting Ubiquinol-Cytochrome c Reductase Core Protein 1 (UQCRC1)

Cited by 9 publications

References 44 publications

Increased Expression of Mitochondrial UQCRC1 in Pancreatic Cancer Impairs Antitumor Immunity of Natural Killer Cells via Elevating Extracellular ATP

Increased Expression of Mitochondrial UQCRC1 in Pancreatic Cancer Impairs Antitumor Immunity of Natural Killer Cells via Elevating Extracellular ATP

Formononetin inhibits osteosarcoma cell proliferation and promotes apoptosis by regulating the miR-214-3p/phosphatase and tensin homolog pathway

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential

Contact Info

Product

Resources

About