miR-193a-5p Promotes Pancreatic Cancer Cell Migration and Invasion Through SRSF6-Mediated Alternative Splicing of OGDHL and ECM1

Li, Manman; Wu, Pandi; Yang, Ziying; Deng, Siwei; Ni, Lingyu; Zhang, Yanfeng; Jin, Liang; Pan, Yi

doi:10.2139/ssrn.3457400

Cited by 34 publications

(45 citation statements)

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“…A previous study reported that microRNAs (miRNAs) could facilitate the AS events of genes [ 37 ]. Therefore, we conducted DE AS gene-miRNAs analysis using DE AS genes and DE miRNA to understand the factors affecting AS events.…”

Section: Resultsmentioning

confidence: 99%

Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes

Zhang

Tang

et al. 2020

Animals

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Previous studies revealed that alternative splicing (AS) events and gene variants played key roles in reproduction; however, their location and distribution in hypothalamic fecundity-related genes in sheep without the FecB mutation remain largely unknown. Therefore, in this study, we described the hypothalamic AS events and variants in differentially expressed genes (DEGs) in Small Tail Han sheep without the FecB mutation at polytocous sheep in the follicular phase vs. monotocous sheep in the follicular phase (PF vs. MF) and polytocous sheep in the luteal phase vs. monotocous sheep in the luteal phase (PL vs. ML) via an RNA-seq study for the first time. We found 39 DEGs with AS events (AS DEGs) in PF vs. MF, while 42 AS DEGs were identified in PL vs. ML. No DEGs with single nucleotide polymorphisms (SNPs) were observed in PF vs. MF, but five were identified in PL vs. ML. We also performed a correlation analysis of transcriptomics and proteomics, and the results suggested several key DEGs/differentially expressed proteins (DEPs), such as galectin 3 (LGALS3) in PF vs. MF and aspartoacylase (ASPA) and transthyretin (TTR) in PL vs. ML, could be candidate genes influencing ovine litter size. In addition, further analyses suggested that AS events, SNPs and miRNA-binding sites existed in key DEGs/DEPs, such as ASPA and TTR. All in all, this study provides a new insight into ovine and even other mammalian reproduction.

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Section: Resultsmentioning

confidence: 99%

Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes

Zhang

Tang

et al. 2020

Animals

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“…Interestingly, miR-193a , with two predicted SBE ( Figure 1B upper panel), was found to be among our list of 1,107 genes. Although previous studies, including ours, have described the epigenetic control and function of miR-193a in several human cancers ( 20 – 22 ), its role in gastric cancer is less explored. We therefore set to examine the functional role of miR-193a in gastric cancer.…”

Section: Resultsmentioning

confidence: 82%

Epigenetic Silencing of STAT3-Targeted miR-193a, by Constitutive Activation of JAK/STAT Signaling, Leads to Tumor Progression Through Overexpression of YWHAZ in Gastric Cancer

et al. 2021

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PurposeThe purpose of this study was to identify genes that were epigenetically silenced by STAT3 in gastric cancer.MethodsMBDcap-Seq and expression microarray were performed to identify genes that were epigenetically silenced in AGS gastric cancer cell lines depleted of STAT3. Cell lines and animal experiments were performed to investigate proliferation and metastasis of miR-193a and YWHAZ in gastric cancer cell lines. Bisulfite pyrosequencing and tissue microarray were performed to investigate the promoter methylation of miR-193a and expression of STAT3, YWHAZ in patients with gastritis (n = 8) and gastric cancer (n = 71). Quantitative methylation-specific PCR was performed to examine miR-193a promoter methylation in cell-free DNA of serum samples in gastric cancer patients (n = 19).ResultsAs compared with parental cells, depletion of STAT3 resulted in demethylation of a putative STAT3 target, miR-193a, in AGS gastric cancer cells. Although bisulfite pyrosequencing and epigenetic treatment confirmed that miR-193a was epigenetically silenced in gastric cancer cell lines, ChIP-PCR found that it may be indirectly affected by STAT3. Ectopic expression of miR-193a in AGS cells inhibited proliferation and migration of gastric cancer cells. Further expression microarray and bioinformatics analysis identified YWHAZ as one of the target of miR-193a in AGS gastric cancer cells, such that depletion of YWHAZ reduced migration in AGS cells, while its overexpression increased invasion in MKN45 cells in vitro and in vivo. Clinically, bisulfite pyrosequencing revealed that promoter methylation of miR-193a was significantly higher in human gastric cancer tissues (n = 11) as compared to gastritis (n = 8, p < 0.05). Patients infected with H. pylori showed a significantly higher miR-193a methylation than those without H. pylori infection (p < 0.05). Tissue microarray also showed a positive trend between STAT3 and YWHAZ expression in gastric cancer patients (n = 60). Patients with serum miR-193a methylation was associated with shorter overall survival than those without methylation (p < 0.05).ConclusionsConstitutive activation of JAK/STAT signaling may confer epigenetic silencing of the STAT3 indirect target and tumor suppressor microRNA, miR-193a in gastric cancer. Transcriptional suppression of miR-193a may led to overexpression of YWHAZ resulting in tumor progression. Targeted inhibition of STAT3 may be a novel therapeutic strategy against gastric cancer.

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“…20,21,24,25 By a series of assays, we demonstrated that MCM3AP-AS1 could bind to miR-193a-5p and inhibit its function. Although Li et al have reported that miR-193a-5p functions as oncogene in pancreatic cancer, 26 other studies demonstrated that miR-193a-5p could inhibit the progression of CRC, and some other cancers. [27][28][29] In this study, we also confirmed that miR-193a-5p serve as a tumor suppressor in CRC and its function could be inhibited by MCM3AP-AS1.…”

Section: Discussionmentioning

confidence: 97%

Long noncoding RNA MCM3AP‐AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR‐193a‐5p/SENP1

et al. 2021

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miR-193a-5p Promotes Pancreatic Cancer Cell Migration and Invasion Through SRSF6-Mediated Alternative Splicing of OGDHL and ECM1

Cited by 34 publications

References 0 publications

Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes

Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes

Epigenetic Silencing of STAT3-Targeted miR-193a, by Constitutive Activation of JAK/STAT Signaling, Leads to Tumor Progression Through Overexpression of YWHAZ in Gastric Cancer

Long noncoding RNA MCM3AP‐AS1 enhances cell proliferation and metastasis in colorectal cancer by regulating miR‐193a‐5p/SENP1

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