Aberrant RNA splicing in thehMSH2 gene: Molecular identification of three aberrant RNA in Scottish patients with colorectal cancer in the West of Scotland

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer. Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers. Methods: It was searched by the PUMUB system and summarized its expression in various cancers. Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased. Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.

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RNA processing genes characterize RNA splicing and further stratify colorectal cancer

Cell Proliferation ◽

10.1111/cpr.12861 ◽

2020 ◽

Vol 53 (8) ◽

Author(s):

Xiaofan Lu ◽

Yujie Zhou ◽

Jialin Meng ◽

Liyun Jiang ◽

Jun Gao ◽

...

Keyword(s):

Colorectal Cancer ◽

Rna Processing ◽

Rna Splicing

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A Common Human β Globin Splicing Mutation Modeled in Mice

Blood ◽

10.1182/blood.v91.6.2152 ◽

1998 ◽

Vol 91 (6) ◽

pp. 2152-2156 ◽

Cited By ~ 52

Author(s):

Jada Lewis ◽

Baoli Yang ◽

Ronald Kim ◽

Halina Sierakowska ◽

Ryszard Kole ◽

...

Keyword(s):

Animal Model ◽

Rna Splicing ◽

Southern China ◽

Embryonic Stem ◽

Mutant Gene ◽

Single Copy ◽

Globin Genes ◽

Globin Chains ◽

Splicing Defects ◽

Aberrant Rna

Abstract The βIVS-2-654 C→T mutation accounts for approximately 20% of β thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to β0 thalassemia. To provide an animal model for testing therapies for correcting splicing defects, we have used the “plug and socket” method of gene targeting in murine embryonic stem cells to replace the two (cis) murine adult β globin genes with a single copy of the human βIVS-2-654 gene. No homozygous mice survive postnatally. Heterozygous mice carrying this mutant gene produce reduced amounts of the mouse β globin chains and no human β globin, and have a moderate form of β thalassemia. The heterozygotes show the same aberrant splicing as their human counterparts and provide an animal model for testing therapies to correct splicing defects at either the RNA or DNA level.

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In Silico Analysis of a Highly Mutated Gene in Cancer Provides Insight into Abnormal mRNA Splicing: Splicing Factor 3B Subunit 1K700E Mutant

Biomolecules ◽

10.3390/biom10050680 ◽

2020 ◽

Vol 10 (5) ◽

pp. 680 ◽

Cited By ~ 2

Author(s):

Asmaa Samy ◽

Baris Suzek ◽

Mehmet Ozdemir ◽

Ozge Sensoy

Keyword(s):

Rna Splicing ◽

In Silico Analysis ◽

Therapy Resistance ◽

Mrna Splicing ◽

Splicing Factor ◽

Cancer Types ◽

Dynamics Simulations ◽

Aberrant Rna ◽

The Impact ◽

Splicing Machinery

Cancer is the second leading cause of death worldwide. The etiology of the disease has remained elusive, but mutations causing aberrant RNA splicing have been considered one of the significant factors in various cancer types. The association of aberrant RNA splicing with drug/therapy resistance further increases the importance of these mutations. In this work, the impact of the splicing factor 3B subunit 1 (SF3B1) K700E mutation, a highly prevalent mutation in various cancer types, is investigated through molecular dynamics simulations. Based on our results, K700E mutation increases flexibility of the mutant SF3B1. Consequently, this mutation leads to i) disruption of interaction of pre-mRNA with SF3B1 and p14, thus preventing proper alignment of mRNA and causing usage of abnormal 3’ splice site, and ii) disruption of communication in critical regions participating in interactions with other proteins in pre-mRNA splicing machinery. We anticipate that this study enhances our understanding of the mechanism of functional abnormalities associated with splicing machinery, thereby, increasing possibility for designing effective therapies to combat cancer at an earlier stage.

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Abstract 4471: Novel SF3B1 deletion mutations result in aberrant RNA splicing in CLL patients

10.1158/1538-7445.am2017-4471 ◽

2017 ◽

Author(s):

Anant A. Agrawal ◽

Michael Seiler ◽

Lindsey Brinton ◽

Rose Mantel ◽

Rosa Lapalombella ◽

...

Keyword(s):

Rna Splicing ◽

Deletion Mutations ◽

Aberrant Rna

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Aberrant RNA Splicing in Cancer

Annual Review of Cancer Biology ◽

10.1146/annurev-cancerbio-030617-050407 ◽

2019 ◽

Vol 3 (1) ◽

pp. 167-185 ◽

Cited By ~ 14

Author(s):

Luisa Escobar-Hoyos ◽

Katherine Knorr ◽

Omar Abdel-Wahab

Keyword(s):

Small Molecules ◽

Rna Splicing ◽

Clinical Development ◽

Splicing Factors ◽

Global Changes ◽

Splicing Regulation ◽

Enzymatic Process ◽

Patients With Cancer ◽

Aberrant Rna

RNA splicing, the enzymatic process of removing segments of premature RNA to produce mature RNA, is a key mediator of proteome diversity and regulator of gene expression. Increased systematic sequencing of the genome and transcriptome of cancers has identified a variety of means by which RNA splicing is altered in cancer relative to normal cells. These findings, in combination with the discovery of recurrent change-of-function mutations in splicing factors in a variety of cancers, suggest that alterations in splicing are drivers of tumorigenesis. Greater characterization of altered splicing in cancer parallels increasing efforts to pharmacologically perturb splicing and early-phase clinical development of small molecules that disrupt splicing in patients with cancer. Here we review recent studies of global changes in splicing in cancer, splicing regulation of mitogenic pathways critical in cancer transformation, and efforts to therapeutically target splicing in cancer.

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