Search

Your search keyword '"MKNK2"' showing total 2 results
Start Over Descriptor "MKNK2" Topic rna splicing
2 results on '"MKNK2"'

1. Dissecting the effects of METTL3 on alternative splicing in prostate cancer.

Author

Lin Wang, Ling Shi, Yonghao Liang, Kin-Wing Ng, Judy, Chan Hoi Yin, Lingyi Wang, Jinpao Hou, Yiwei Wang, Sin-Hang Fung, Cathy, Ka-Fung Chiu, Peter, Chi-Fai Ng, and Kwok-Wing Tsui, Stephen

Subjects
ALTERNATIVE RNA splicing, PROSTATE cancer, RNA splicing, RNA sequencing, CELL lines
Abstract

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3- regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

2. SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma

Author

Hongda Liu, Zheng Gong, Qun Zhang, Zekuan Xu, Yunfei Xu, and Kangshuai Li

Subjects
0301 basic medicine, Male, MKNK2, Cancer Research, Mice, Nude, Biology, SRPK1, Adenocarcinoma, Protein Serine-Threonine Kinases, medicine.disease_cause, lcsh:RC254-282, 03 medical and health sciences, Splicing factor, Mice, 0302 clinical medicine, medicine, Animals, Humans, Phosphorylation, Colon adenocarcinoma, Gene, Cell Proliferation, Serine-Arginine Splicing Factors, Kinase, Research, Alternative splicing, Intracellular Signaling Peptides and Proteins, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Receptors, Neuropeptide Y, SRSF1, Alternative Splicing, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, RNA splicing, Colonic Neoplasms, Cancer research, Carcinogenesis, SRPK1/2
Abstract

Background The Mnk2 kinase, encoded by MKNK2 gene, plays critical roles in MAPK signaling and was involved in oncogenesis. Human MKNK2 pre-mRNA can be alternatively spliced into two splicing isoforms, the MKNK2a and MKNK2b, thus yielding Mnk2a and Mnk2b proteins with different domains. The involvement of Mnk2 alternative splicing in colon cancer has been implicated based on RNA-sequencing data from TCGA database. This study aimed at investigating the upstream modulators and clinical relevance of Mnk2 alternative splicing in colon adenocarcinoma (CAC). Methods PCR, western blotting and immunohistochemistry (IHC) were performed to assess the expression of Mnk2 and upstream proteins in CAC. The function of Mnk2 and its regulators were demonstrated in different CAC cell lines as well as in xenograft models. Two independent cohorts of CAC patients were used to reveal the clinical significance of MKNK2 alternative splicing. Results Comparing with adjacent nontumorous tissue, CAC specimen showed a decreased MKNK2a level and an increased MKNK2b level, which were correlated with KRAS mutation and tumor size. The SRSF1 (serine/arginine-rich splicing factor 1) was further confirmed to be the major splicing factor targeting MKNK2 in CAC cells. Higher expression of SRPK1/2 or decreased activity of PP1α were responsible for enhancing SRSF1 phosphorylation and nucleus translocation, subsequently resulted in a switch of MKNK2 alternative splicing. Conclusions Our data showed that phosphorylation and subcellular localization of SRSF1 were balanced by SRPK1/2 and PP1α in CAC cells. High nucleus SRSF1 promoted MKNK2 splicing into MKNK2b instead of MNK2a, consequently enhanced tumor proliferation.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results