ALKBH5 Holds Prognostic Values and Inhibits the Metastasis of Colon Cancer

Yang, Peipei; Wang, Qian; Liu, Aihua; Zhu, Jun; Feng, Jinzhou

doi:10.1007/s12253-019-00737-7

Cited by 64 publications

(63 citation statements)

References 25 publications

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“…According to recent studies, ALKBH5 plays an important role in the occurrence and development of cancer in human [6,7]. For example, ALKBH5 holds prognostic value and inhibits the metastasis of colon cancer [8]; ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of Cyr61 mRNA [9]; METTL3 and ALKBH5 oppositely regulate m 6 A modification of TFEB mRNA, dictating the fate of hypoxia/reoxygenation-treated cardiomyocyte [10]; ALKBH5 inhibits pancreatic cancer cell motility by decreasing methylation of the long non-coding RNA KCNK15-AS1 [11]. Moreover, HuR restrains translation inhibition mediated by some miRNAs by directly binding and sequestering microRNAs (miRNAs).…”

Section: Introductionmentioning

confidence: 99%

m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC

et al. 2020

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Background: The importance of mRNA methylation erased by ALKBH5 in mRNA biogenesis, decay, and translation control is an emerging research focus. Ectopically activated YAP is associated with the development of many human cancers. However, the mechanism whereby ALKBH5 regulates YAP expression and activity to inhibit NSCLC tumor growth and metastasis is not clear. Methods: Protein and transcript interactions were analyzed in normal lung cell and NSCLC cells. Gene expression was evaluated by qPCR and reporter assays. Protein levels were determined by immunochemical approaches. Nucleic acid interactions and status were analyzed by immunoprecipitation. Cell behavior was analyzed by standard biochemical tests. The m 6 A modification was analyzed by MeRIP. Results: Our results show that YAP expression is negatively correlated with ALKBH5 expression and plays an opposite role in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. ALKBH5 reduced m 6 A modification of YAP. YTHDF3 combined YAP pre-mRNA depending on m 6 A modification. YTHDF1 and YTHDF2 competitively interacted with YTHDF3 in an m 6 A-independent manner to regulate YAP expression. YTHDF2 facilitated YAP mRNA decay via the AGO2 system, whereas YTHDF1 promoted YAP mRNA translation by interacting with eIF3a; both these activities are regulated by m 6 A modification. Furthermore, ALKBH5 decreased YAP activity by regulating miR-107/LATS2 axis in an HuR-dependent manner. Further, ALKBH5 inhibited tumor growth and metastasis in vivo by reducing the expression and activity of YAP. Conclusions: The presented findings suggest m 6 A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Moreover, effective inhibition of m 6 A modification of ALKBH5 might constitute a potential treatment strategy for lung cancer.

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Section: Introductionmentioning

confidence: 99%

m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC

et al. 2020

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“…Notably, decreased ALKBH5 was closely connected with a shortened overall and cancer-specific survival following nephrectomy in ccRCC [45]. What's more, decreased expression of ALKBH5 was closely associated with metastasis and American Joint Committee on Cancer (AJCC) stage and acted as an independent prognostic indicator in colon cancer patients [17]. Tang, et al [16] found that low level of ALKBH5 predicted poor clinical outcome in pancreatic ductal adenocarcinoma, phenochromocytoma, paraganglioma, stomach adenocarcinoma and uterine corpus endometrial carcinoma.…”

Section: Alkbh5 In Cancer Prognosismentioning

confidence: 94%

“…It was found that ALKBH5 sensitized pancreatic ductal adenocarcinoma (PDAC) cells to chemotherapy and ALKBH5 remarkably inhibits pancreatic ductal adenocarcinoma cell proliferation, migration, and invasion, partly by altering the expression of Wnt inhibitory factor 1 (WIF-1), which is mediation of the Wnt pathway [16]. ALKBH5 was downregulated in colon cancer tissues, and the overexpression of ALKBH5 greatly reatrained colon cancer cells invasion in vitro and metastasis in vivo [17]. Besides, ALKBH5 participated in the carcinogenicity of gastric cancer by affecting the methylation of NEAT1 [19].…”

Section: Alkbh5 In Gastrointestinal Cancermentioning

confidence: 99%

“…Recently, the effects of ALKBH5 on many biological processes had been demonstrated, including proliferation [11], invasion [12], metastasis [13], ossification [14] and so on. In addition, ALKBH5 was also involved in kinds of cancers or noncancers, such as glioblastoma [15], pancreatic cancer [16], colon cancer [17], breast cancer [18], gastric cancer [19], lung cancer [20], ovarian cancer [21], diabetes [22] and reproductive system diseases [23] (Figs. 1, 2).…”

Section: Introductionmentioning

confidence: 99%

“…In the field of cancer research, the underlying mechanisms of ALKBH5 in human cancers were not only unclear but also controversial. Up to date, the expression of ALKBH5 was up-regulated or down-regulated in various cancers, and played an oncogenic or tumor suppressive role in breast cancer, gastric cancer, colon cancer and so on [17,19,24]. The potential mechanisms were involved with long non-coding RNAs, miRNAs, mRNA and so on [19,21,24].…”

Section: Introductionmentioning

confidence: 99%

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The biological function of m6A demethylase ALKBH5 and its role in human disease

Wang

Wang²,

et al. 2020

Cancer Cell Int

134

113

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Human AlkB homolog H5 (ALKBH5) is a primary m6A demethylase, which is dysregulated and acts as a biological and pharmacological role in human cancers or non-cancers. ALKBH5 plays a dual role in various cancers through regulating kinds of biological processes, such as proliferation, migration, invasion, metastasis and tumor growth. In addition, it takes a great part in human non-cancer, including reproductive system diseases. The underlying regulatory mechanisms of ALKBH5 that relys on m6A-dependent modification are implicated with long non-coding RNA, cancer stem cell, autophagy and hypoxia. ALKBH5 is also an independent prognostic indicator in various cancers. In this review, we summarized the current evidence on ALKBH5 in diverse human cancers or non-cancers and its potential as a prognostic target.

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Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

Guan,

Wong

2024

Cancer Medicine

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The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising RNA methylation have been identified. Notably, these m6A regulators often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, the complex roles of these regulators in human cancer pathology remain enigmatic, with conflicting outcomes reported in different studies.In recent years, a multitude of inhibitors and activators targeting m6A regulators have been reported. Several of these compounds have demonstrated promising efficacy in both in vitro and in vivo cancer models. These findings collectively underscore the dynamic landscape of m6A regulation in cancer biology, revealing its potential as a therapeutic target and prognostic indicator.

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ALKBH5 Holds Prognostic Values and Inhibits the Metastasis of Colon Cancer

Cited by 64 publications

References 25 publications

m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC

m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2–mediated YAP activity in NSCLC

The biological function of m6A demethylase ALKBH5 and its role in human disease

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

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