ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner

Li, Luyao; Wang, Qin; Pan, Shuya; Hou, Yaxuan; Xia, Jiamin; Zhou, Xue

doi:10.1016/j.ecoenv.2021.112686

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…Li et al showed that the global level of mRNA m6A modification was significantly decreased in Cd-transformed BEAS-2B cells, mediated by Cd-induced up-regulation of alkB homolog 5, RNA demethylase (ALKBH5), an m6A demethylase [ 242 ]. Furthermore, ALKBH5 promoted the proliferation, migration, invasion, and anchorage-independent growth of transformed BEAS-2B cells by reducing the m6A level of phosphatase and tensin homolog (PTEN) mRNA via demethylating m6A in PTEN mRNA, resulting in its instability and the reduction in PTEN protein expression [ 242 ]. These results suggest that ALKBH5 promotes Cd-induced carcinogenesis by reducing PTEN mRNA stability in an m6A-dependent manner [ 242 ].…”

Section: Cadmium (Cd)mentioning

confidence: 99%

“…Furthermore, ALKBH5 promoted the proliferation, migration, invasion, and anchorage-independent growth of transformed BEAS-2B cells by reducing the m6A level of phosphatase and tensin homolog (PTEN) mRNA via demethylating m6A in PTEN mRNA, resulting in its instability and the reduction in PTEN protein expression [ 242 ]. These results suggest that ALKBH5 promotes Cd-induced carcinogenesis by reducing PTEN mRNA stability in an m6A-dependent manner [ 242 ]. In Cd-transformed SV-HUC-1 human uroepithelial cells, Cd caused global changes in mRNA and protein expression and m6A-modified genes.…”

Section: Cadmium (Cd)mentioning

confidence: 99%

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Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

Zhao

Islam

Wang

et al. 2022

Cancers

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Environmental and occupational exposure to heavy metals, such as hexavalent chromium, nickel, and cadmium, are major health concerns worldwide. Some heavy metals are well-documented human carcinogens. Multiple mechanisms, including DNA damage, dysregulated gene expression, and aberrant cancer-related signaling, have been shown to contribute to metal-induced carcinogenesis. However, the molecular mechanisms accounting for heavy metal-induced carcinogenesis and angiogenesis are still not fully understood. In recent years, an increasing number of studies have indicated that in addition to genotoxicity and genetic mutations, epigenetic mechanisms play critical roles in metal-induced cancers. Epigenetics refers to the reversible modification of genomes without changing DNA sequences; epigenetic modifications generally involve DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs. Epigenetic regulation is essential for maintaining normal gene expression patterns; the disruption of epigenetic modifications may lead to altered cellular function and even malignant transformation. Therefore, aberrant epigenetic modifications are widely involved in metal-induced cancer formation, development, and angiogenesis. Notably, the role of epigenetic mechanisms in heavy metal-induced carcinogenesis and angiogenesis remains largely unknown, and further studies are urgently required. In this review, we highlight the current advances in understanding the roles of epigenetic mechanisms in heavy metal-induced carcinogenesis, cancer progression, and angiogenesis.

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Section: Cadmium (Cd)mentioning

confidence: 99%

Section: Cadmium (Cd)mentioning

confidence: 99%

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

Zhao

Islam

Wang

et al. 2022

Cancers

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“…Li et al reported that the protein level of the m6A eraser ALKBH5 was up-regulated, and the total mRNA m6A modification levels were significantly reduced in cadmium-transformed human bronchial epithelial BEAS-2B cells [ 68 ]. Knockdown of ALKBH5 in cadmium-transformed BEAS-2B cells not only up-regulated total mRNA m6A levels but also reduced their transformed phenotypes, as evidenced by the decreased proliferation, migration, invasion, and anchorage-independent growth [ 68 ]. The tumor suppressor gene PTEN was identified as a target gene of ALKBH5.…”

Section: Epitranscriptomic Mechanisms Of Metal Toxicity and Carcinoge...mentioning

confidence: 99%

“…It was determined that ALKBH5 reduced the m6A modification level of PTEN mRNA, leading to its instability and decrease in PTEN protein expression. Simultaneous knockdown of both ALKBH5 and PTEN reversed the inhibitory effect of ALKBH5 knockdown alone on the transformed phenotypes of cadmium-transformed cells [ 68 ]. These findings suggest that chronic cadmium exposure up-regulates ALKBH5 expression to reduce tumor suppressor gene PTEN mRNA m6A modification, down-regulating PTEN expression to promote cell transformation.…”

Section: Epitranscriptomic Mechanisms Of Metal Toxicity and Carcinoge...mentioning

confidence: 99%

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

Yang

Wang

2022

IJMS

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Metals are common toxic environmental pollutants. Acute or chronic exposure to metal pollutants causes severe adverse health effects in animals and humans, such as developmental retardation, abnormal metabolism, and disorders of cardiovascular, neurologic, respiratory, reproductive, and urologic systems. Moreover, several metals (arsenic, cadmium, chromium, and nickel) are classified as potent Group I carcinogens and cause various types of cancer in humans. Although the toxicity and carcinogenicity of metal pollutants are well recognized, the underlying mechanisms have not been clearly defined. The epitranscriptome includes all kinds of chemical modifications of all forms of RNA molecules inside a cell. Recent progresses in demonstrating the reversible pattern of RNA modifications and their roles in physiology and pathogenesis represent a breakthrough in the field of RNA biology and function study. The epitranscriptomic study is now an exciting emerging field in toxicology research. While few studies have been conducted so far to determine the epitranscriptomic effects of metal pollutants, they offer novel insights for understanding the mechanisms of metal toxicity and carcinogenesis. The goal of this review is to discuss recent studies on the epitranscriptomic effects of metals and propose some thoughts for future studies in the field.

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“…M6A methylation is also demethylated by the FTO and AlkB homolog 5 (ALKBH5) demethylases ( Ye et al, 2021 ). M6A modification is involved in all mRNA metabolic processes, including maturation, transport, splicing, translation, and degradation ( Song et al, 2020 ; Li et al, 2021b Li et al, 2021c ; Lou et al, 2021 ). M6A RNA methylation exerts critical biological functions in mammals, such as tissue development, circadian rhythms, DNA damage responses, gender identification, and tumor occurrence and development ( Xu et al, 2020a ; Li et al, 2020 ; Ma and Ji 2020 ; Gu et al, 2021b ; Wu and Wang 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Liu

2022

Front. Genet.

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N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

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ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner

Cited by 19 publications

References 42 publications

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

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