Mitochondria‑related TFAM gene variants and their effects on patients with cervical cancer

Golubickaitė, Ieva; Ugenskienė, Rasa; Čepaitė, Justė; Žilienė, Eglė; Inčiūra, Arturas; Poškienė, Lina; Juozaitytė, Elona

doi:10.3892/br.2021.1482

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…Further studies are required to investigate whether the expression of genes involved in mitochondrial biogenesis and celecoxib-induced loss of ΔΨ m could be rescued by TMEM117 overexpression. Interestingly, TFAM expression is reportedly altered in and associated with breast and lung cancer; additionally, polymorphisms in TFAM are reportedly associated with a variety of cancers [49,[52][53][54][55][56][57][58]. UCP2 expression is also involved in cancer [59][60][61].…”

Section: Discussionmentioning

confidence: 99%

Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer

Maruyama

Kiyohara

Kudo

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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The anti-in ammatory drug celecoxib, the only inhibitor of cyclooxygenase-2 (COX-2) with anticancer activity, is used to treat rheumatoid arthritis and can cause endoplasmic reticulum (ER) stress by inhibiting sarco/ER Ca 2 + -ATPase activity in cancer cells. This study aimed to investigate the correlation between celecoxib-induced ER stress and the effects of celecoxib against cell death signaling. Treatment of human colon cancer HCT116 cells with celecoxib reduced their viability and resulted in a loss of mitochondrial membrane potential (ΔΨ m ). Additionally, celecoxib treatment reduced the expression of genes involved in mitochondrial biogenesis and metabolism such as mitochondrial transcription factor A (TFAM) and uncoupling protein 2 (UCP2). Furthermore, celecoxib reduced transmembrane protein 117 (TMEM117) and RNAi-mediated knockdown of TMEM117 reduced TFAM and UCP2 expression. These results suggest that celecoxib treatment results in loss of ΔΨ m by reducing TMEM117 expression and provide insights for the development of novel drugs through TMEM117 expression.

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Section: Discussionmentioning

confidence: 99%

Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer

Maruyama

Kiyohara

Kudo

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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“…The cancer cell stage and the type of genetic alterations can impact the tumourigenic role of mitochondrial Ca 2+ dysregulation (Marchi, Vitto, et al., 2019). Enhanced mtCU activity has been linked with colorectal cancer (CRC) (Golubickaite et al., 2021; Li et al., 2014; Liu et al., 2020; Zeng et al., 2018; Zhu et al., 2023), breast cancer (Curry et al., 2013; Hall et al., 2014; Tosatto et al., 2016; Yu et al., 2017), OSCC (Fan et al., 2017; Liu et al., 2008; Zheng et al., 2017, 2022), pancreatic cancer (Chen et al., 2017; Long et al., 2015; Wang et al., 2022; Yang et al., 2019), hepatocellular carcinoma (HCC) (Jin et al., 2019; Li, Lin, et al., 2020; Martin et al., 2006; Ren et al., 2017; Wang et al., 2015) and embryonal rhabdomyosarcoma (ERMS) (Chiu et al., 2022). By contrast, decreased mtCU activity has been associated with melanoma (Stejerean‐Todoran et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

“…MCU protein levels are positively correlated with mitochondrial transcription factor A (TFAM) expression, a nuclear‐encoded protein involved in mitochondrial biogenesis (Golubickaite et al., 2021) in CRC tissues (Liu et al., 2020) (Table 2). Downregulation of MCU lead to TFAM degradation and impaired mitochondrial biogenesis as a result of enhanced phosphorylation at TFAM S55, whereas MCU overexpression promoted TFAM dephosphorylation (Liu et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

The mitochondrial calcium uniporter: Balancing tumourigenic and anti‐tumourigenic responses

Colussi,

Stathopulos

2024

The Journal of Physiology

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Increased malignancy and poor treatability associated with solid tumour cancers have commonly been attributed to mitochondrial calcium (Ca2+) dysregulation. The mitochondrial Ca2+ uniporter complex (mtCU) is the predominant mode of Ca2+ uptake into the mitochondrial matrix. The main components of mtCU are the pore‐forming mitochondrial Ca2+ uniporter (MCU) subunit, MCU dominant‐negative beta (MCUb) subunit, essential MCU regulator (EMRE) and the gatekeeping mitochondrial Ca2+ uptake 1 and 2 (MICU1 and MICU2) proteins. In this review, we describe mtCU‐mediated mitochondrial Ca2+ dysregulation in solid tumour cancer types, finding enhanced mtCU activity observed in colorectal cancer, breast cancer, oral squamous cell carcinoma, pancreatic cancer, hepatocellular carcinoma and embryonal rhabdomyosarcoma. By contrast, decreased mtCU activity is associated with melanoma, whereas the nature of mtCU dysregulation remains unclear in glioblastoma. Furthermore, we show that numerous polymorphisms associated with cancer may alter phosphorylation sites on the pore forming MCU and MCUb subunits, which cluster at interfaces with EMRE. We highlight downstream/upstream biomolecular modulators of MCU and MCUb that alter mtCU‐mediated mitochondrial Ca2+ uptake and may be used as biomarkers or to aid in the development of novel cancer therapeutics. Additionally, we provide an overview of the current small molecule inhibitors of mtCU that interact with the Asp residue of the critical Asp‐Ile‐Met‐Glu motif or through other allosteric regulatory mechanisms to block Ca2+ permeation. Finally, we describe the relationship between MCU‐ and MCUb‐mediating microRNAs and mitochondrial Ca2+ uptake that should be considered in the discovery of new treatment approaches for cancer. image

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Association Between Potentially Functional Variants in chr5q14 and the Risk of Cervical Cancer in a Chinese Population

Liu

Chen

et al. 2022

Reprod. Sci.

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Mitochondria‑related TFAM gene variants and their effects on patients with cervical cancer

Cited by 7 publications

References 23 publications

Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer

Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer

The mitochondrial calcium uniporter: Balancing tumourigenic and anti‐tumourigenic responses

Association Between Potentially Functional Variants in chr5q14 and the Risk of Cervical Cancer in a Chinese Population

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