Histone methyltransferase and drug resistance in cancers

Yang, Cheng Chieh; Zhang, Jiayu; Ma, Yukui; Wu, Chunfu; Cui, Wei; Wang, Lihui

doi:10.1186/s13046-020-01682-z

Cited by 55 publications

(42 citation statements)

References 104 publications

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“…Furthermore, the emergence of drug resistance is another challenge in cancer treatment, which is closely related to epigenetics chances. 29 Therefore, the HMTs have become an important target group for the development of new cancer control methodology. 30 Here, we present several changes of the genetic signature of 10 HMTs as a genetic atlas to provide new information about HMTs and GC to aim of assisting in the developing of new strategies to control this cancer type.…”

Section: Discussionmentioning

confidence: 99%

Histone Methyltransferases Useful in Gastric Cancer Research

Reyes

Sarría²,

Salazar-Viedma

et al. 2021

Cancer Inform

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Gastric cancer (GC) is one of the most frequent tumors in the world. Stomach adenocarcinoma is a heterogeneous tumor, turning the prognosis prediction and patients’ clinical management difficult. Some diagnosis tests for GC are been development using knowledge based in polymorphisms, somatic copy number alteration (SCNA) and aberrant histone methylation. This last event, a posttranslational modification that occurs at the chromatin level, is an important epigenetic alteration seen in several tumors including stomach adenocarcinoma. Histone methyltransferases (HMT) are the proteins responsible for the methylation in specific amino acids residues of histones tails. Here, were presented several HMTs that could be relating to GC process. We use public data from 440 patients with stomach adenocarcinoma. We evaluated the alterations as SCNAs, mutations, and genes expression level of HMTs in these aforementioned samples. As results, it was identified the 10 HMTs most altered (up to 30%) in stomach adenocarcinoma samples, which are the PRDM14, PRDM9, SUV39H2, NSD2, SMYD5, SETDB1, PRDM12, SUV39H1, NSD3, and EHMT2 genes. The PRDM9 gene is among most mutated and amplified HMTs within the data set studied. PRDM14 is downregulated in 79% of the samples and the SUV39H2 gene is down expressed in patients with recurred/progressed disease. Several HMTs are altered in many cancers. It is important to generate a genetic atlas of alterations of cancer-related genes to improve the understanding of tumorigenesis events and to propose novel tools of diagnosis and prognosis for the cancer control.

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Section: Discussionmentioning

confidence: 99%

Histone Methyltransferases Useful in Gastric Cancer Research

Reyes

Sarría²,

Salazar-Viedma

et al. 2021

Cancer Inform

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“…EMT results in changes in cell morphology associated with alterations in epithelial and mesenchymal markers expression 42 . EMT like phenotype has been reported in chemoresistant variant cell lines generated upon multiple rounds of chemotherapy treatment such as; cisplatin resistant ovarian cancer cells (TOV-112D, MDAH, OVSAHO, SKOV-3/DDP, OVCAR3/DDP and A2780CP) [43][44][45][46] , A2780/PTX, NOS-PR, TAOV-PR, and SKOV-PR paclitaxel resistant ovarian cancer cells 20,21 . Also, chemotherapeutic resistance promotes EMT like changes in other cancer cell lines, including non-small cell lung cancer 15,16 , gastric cancer 14 nasopharyngeal carcinoma cells 17 , and breast cancer cells 18,19 .…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Role of CpG Methylation in Epithelial Mesenchymal Transition Master Genes in a Chemoresistant Ovarian Cancer Cell line

Alghamian

Soukkarieh

Abbady

et al. 2021

Preprint

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Ovarian cancer is one of the commonly diagnosed cancers among women. Chemoresistant is an essential reason for treatment failure and high mortality. Emerging evidence connects epithelial mesenchymal transition (EMT) like changes and acquisition of chemoresistance in cancer. DNA methylation influences cellular processes including EMT. Here, we investigate EMT like changes in cisplatin-resistant A2780 ovarian cancer cells (A2780cis), and we study the DNA methylation role in EMT master genes regulation. Cell viability assay was carried to test the sensitivity of A2780, and A2780cis human cancer cell lines to cisplatin compared to other cancer cell lines. Differential mRNA expression of EMT markers using qPCR was conducted to investigate EMT like changes. The role of CpGs methylation in gene expression regulation was investigated by 5-azacytidine (5-aza) treatment. DNA methylation changes in EMT genes were identified using Methylscreen assay between A2780 and A2780cis cells. A2780cis maintains its cisplatin tolerance ability and exhibits phenotypic changes congruent with EMT. Methylscreen assay and qPCR study revealed DNA hypermethylation in promoters of epithelial adhesion molecules CDH1 and EPCAM in A2780cis compared to the cisplatin-sensitive parental cells, these changes were concomitant with gene expression down-regulation. DNA hypomethylation associated with transcription up-regulation of the mesenchymal marker TWIST2 was observed in the resistant cells. Azacytidine treatment confirmed the DNA methylation role in the regulation of gene expression of CDH1, EPCAM and TWIST2 genes. A2780cis cell line undergoes EMT like changes, and EMT master genes are regulated by DNA methylation. A better perception of the molecular alterations which correlate with chemoresistance may lead to therapeutic benefits such as chemosensitivity restoration.

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“…Cancer drug resistance accounts for approximately 90% of cancer-related mortality [ 43 , 44 , 45 ]. There is overwhelming evidence that epigenetic modifications represent a potential mechanism for rapid acquisition of drug resistance in cancer [ 34 , 46 , 47 , 48 , 49 ]. Similar to other cancers, GBM cells can acquire resistance to drug therapy through multiple mechanisms.…”

Section: Epigenetic Alteration Involved In Drug Resistance Of Gbmmentioning

confidence: 99%

The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

Berglund

Etame

2021

IJMS

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Glioblastoma (GBM) is a highly lethal cancer that is universally refractory to the standard multimodal therapies of surgical resection, radiation, and chemotherapy treatment. Temozolomide (TMZ) is currently the best chemotherapy agent for GBM, but the durability of response is epigenetically dependent and often short-lived secondary to tumor resistance. Therapies that can provide synergy to chemoradiation are desperately needed in GBM. There is accumulating evidence that adaptive resistance evolution in GBM is facilitated through treatment-induced epigenetic modifications. Epigenetic alterations of DNA methylation, histone modifications, and chromatin remodeling have all been implicated as mechanisms that enhance accessibility for transcriptional activation of genes that play critical roles in GBM resistance and lethality. Hence, understanding and targeting epigenetic modifications associated with GBM resistance is of utmost priority. In this review, we summarize the latest updates on the impact of epigenetic modifications on adaptive resistance evolution in GBM to therapy.

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Histone methyltransferase and drug resistance in cancers

Cited by 55 publications

References 104 publications

Histone Methyltransferases Useful in Gastric Cancer Research

Histone Methyltransferases Useful in Gastric Cancer Research

Investigation of the Role of CpG Methylation in Epithelial Mesenchymal Transition Master Genes in a Chemoresistant Ovarian Cancer Cell line

The Impact of Epigenetic Modifications on Adaptive Resistance Evolution in Glioblastoma

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