YTHDF2 promotes intrahepatic cholangiocarcinoma progression and desensitises cisplatin treatment by increasing CDKN1B mRNA degradation

Huang, Chen‐Song; Zhu, Ying-Qin; Xu, Qiong‐Cong; Chen, Siyun; Huang, Yue; Zhao, Guochao; Ni, Xiao; Liu, Bo; Zhao, Wei; Yin, Xiao‐Yu

doi:10.1002/ctm2.848

Cited by 43 publications

(26 citation statements)

References 42 publications

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“…Cisplatin promotes tumor cell apoptosis by forming an adduct with the DNA of tumor cells, thereby achieving its anti-tumor effect [ 32 ]. Many studies have confirmed that the decrease in cell cycle arrest is the key factor in tumor cisplatin resistance [ 33 , 34 , 35 ]. We found that the overexpression of miR - 660 decreased the cell proliferation capacity and increased the cell apoptosis rate and cell cycle arrest in cisplatin-treated A549/CDDP and CALU-3 cells.…”

Section: Discussionmentioning

confidence: 99%

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

Wang

Zhou

Chen

et al. 2023

Genes

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Increasing evidence suggests that microRNAs’ (miRNAs) abnormal expression is one of the main factors of chemotherapy resistance in various cancers. However, the role of miRNAs in lung adenocarcinoma (LUAD) resistance to cisplatin is still unclear. In this study, we analyzed a microarray dataset to investigate miRNAs related to cisplatin resistance in LUAD. The expression of miRNAs in LUAD tissues and cell lines was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Special AT-Rich Sequence-Binding Protein 2 (SATB2) in LUAD cell lines was detected using RT-qPCR and Western blot. Cell proliferation was measured by CCK8 and colony formation assays, while cell cycle and apoptosis were measured by flow cytometry. A dual-luciferase reporter assay was performed to confirm that SATB2 is a target gene of microRNA-660 (miR-660). We showed that the expression of miR-660 was not only decreased in LUAD cells and tissues but also further decreased in the cisplatin-resistant A549 cell line. The overexpression of miR-660 increased cisplatin sensitivity in LUAD cells. In addition, we identified SATB2 as a direct target gene of miR-660. We also revealed that miR-660 increased cisplatin sensitivity in LUAD cells via targeting SATB2. In conclusion, miR-660/SATB2 axis is a key regulator of cisplatin resistance in LUAD.

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Section: Discussionmentioning

confidence: 99%

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

Wang

Zhou

Chen

et al. 2023

Genes

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“…In addition, YTHDF1 and YTHDF2 facilitate the advancement of intrahepatic cholangiocarcinoma (ICC) through increasing EGFR mRNA translation and IFIT2 mRNA decay, respectively ( 188 , 189 ). Meanwhile, YTHDF2 silencing restrains ICC resistance to the exposure of cisplatin by reversing the degradation of cyclin-dependent kinase inhibitor 1B (CDKN1B) mRNA ( 190 ).…”

Section: The Role Of the Ythdf Family In Cancersmentioning

confidence: 99%

N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

Chen

Gao

et al. 2023

Front. Immunol.

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As the most abundant and conserved internal modification in eukaryote RNAs, N6-methyladenosine (m6A) is involved in a wide range of physiological and pathological processes. The YT521-B homology (YTH) domain-containing family proteins (YTHDFs), including YTHDF1, YTHDF2, and YTHDF3, are a class of cytoplasmic m6A-binding proteins defined by the vertebrate YTH domain, and exert extensive functions in regulating RNA destiny. Distinct expression patterns of the YTHDF family in specific cell types or developmental stages result in prominent differences in multiple biological processes, such as embryonic development, stem cell fate, fat metabolism, neuromodulation, cardiovascular effect, infection, immunity, and tumorigenesis. The YTHDF family mediates tumor proliferation, metastasis, metabolism, drug resistance, and immunity, and possesses the potential of predictive and therapeutic biomarkers. Here, we mainly summary the structures, roles, and mechanisms of the YTHDF family in physiological and pathological processes, especially in multiple cancers, as well as their current limitations and future considerations. This will provide novel angles for deciphering m6A regulation in a biological system.

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“…ALKBH5-mediated m 6 A demethylation stabilizes CASC8 transcription, ultimately leading to cisplatin resistance in ESCC [120]. Furthermore, YTHDF2 increased CDKN1B mRNA degradation in an m 6 A-dependent manner, which promoted intrahepatic cholangiocarcinoma (ICC) progression and reduced sensitivity to cisplatin treatment [121]. m 6 A modifications also play an integral part in tamoxifen resistance, a classical chemotherapeutic agent in breast cancer treatment [122].…”

Section: Induced Specific Drug Resistancementioning

confidence: 99%

Biological and pharmacological roles of m6A modifications in cancer drug resistance

et al. 2022

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Cancer drug resistance represents the main obstacle in cancer treatment. Drug-resistant cancers exhibit complex molecular mechanisms to hit back therapy under pharmacological pressure. As a reversible epigenetic modification, N6-methyladenosine (m6A) RNA modification was regarded to be the most common epigenetic RNA modification. RNA methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) are frequently disordered in several tumors, thus regulating the expression of oncoproteins, enhancing tumorigenesis, cancer proliferation, development, and metastasis. The review elucidated the underlying role of m6A in therapy resistance. Alteration of the m6A modification affected drug efficacy by restructuring multidrug efflux transporters, drug-metabolizing enzymes, and anticancer drug targets. Furthermore, the variation resulted in resistance by regulating DNA damage repair, downstream adaptive response (apoptosis, autophagy, and oncogenic bypass signaling), cell stemness, tumor immune microenvironment, and exosomal non-coding RNA. It is highlighted that several small molecules targeting m6A regulators have shown significant potential for overcoming drug resistance in different cancer categories. Further inhibitors and activators of RNA m6A-modified proteins are expected to provide novel anticancer drugs, delivering the therapeutic potential for addressing the challenge of resistance in clinical resistance.

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YTHDF2 promotes intrahepatic cholangiocarcinoma progression and desensitises cisplatin treatment by increasing CDKN1B mRNA degradation

Cited by 43 publications

References 42 publications

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

Biological and pharmacological roles of m6A modifications in cancer drug resistance

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