Dataset Information

Modification of STIM2 by m⁶A RNA methylation inhibits metastasis of cholangiocarcinoma.

ABSTRACT:

Background

N6-methyladenosine (m⁶A) is the most frequent internal methylation of eukaryotic RNA (ribonucleic acid) transcripts and plays an important function in RNA processing. The current research aimed to investigate the role of m⁶A-STIM2 axis in cholangiocarcinoma (CCA) progression.

Methods

The expression of STIM2 (Stromal Interaction Molecule 2) in CCA was measured using quantitative polymerase chain reaction (PCR) and immunohistochemistry (IHC). STIM2 was examined in vivo for its effects on the malignant phenotypes of CCA cells. The m⁶A modification of STIM2 was assessed through MeRIP (methylated RNA Immunoprecipitation)-PCR.

Results

Based on the GEPIA (Gene Expression Profiling Interactive Analysis) 2 database findings, a low STIM2 mRNA (messenger RNA) level was related to a poor prognosis in individuals with CCA. Quantitative PCR and IHC assays indicated decreased protein satin in CCA tissues and were associated with extrahepatic metastasis. Vianude mice tail vein injection model indicated that increased STIM2 levels suppressed CCA cell metastasis in vivo, while KRT8 (keratin 8) was detected as the direct downstream target of STIM2-mediated CCA cell metastasis in vivo. Meanwhile, based on SRAMP database and MeRIP assays indicated that m⁶A alteration resulted in abnormal STIM2 expression in CCA via METTL14 and YTHDC2.

Conclusions

Our findings revealed the epi-transcriptomic dysregulation in CCA and metastasis by proposing a complicated STIM2-KRT8 regulatory paradigm based on m⁶A alteration.

SUBMITTER: Chen FQ

PROVIDER: S-EPMC8848379 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modification of STIM2 by m<sup>6</sup>A RNA methylation inhibits metastasis of cholangiocarcinoma.

Chen Feng-Qiu FQ Zheng Hao H Gu Ting T Hu Yu-Hua YH Yang Le L Huang Zhi-Ping ZP Qiao Guang-Lei GL Li Hong-Jie HJ

Annals of translational medicine 20220101 2

<h4>Background</h4>N6-methyladenosine (m<sup>6</sup>A) is the most frequent internal methylation of eukaryotic RNA (ribonucleic acid) transcripts and plays an important function in RNA processing. The current research aimed to investigate the role of m<sup>6</sup>A-STIM2 axis in cholangiocarcinoma (CCA) progression.<h4>Methods</h4>The expression of STIM2 (Stromal Interaction Molecule 2) in CCA was measured using quantitative polymerase chain reaction (PCR) and immunohistochemistry (IHC). STIM2 w ...[more]

PMID: 35282134

Similar Datasets

Project description:BackgroundThere is growing evidence to demonstrate that the epigenetic regulation of immune characteristics, especially for N6-methyladenosine (m6A) RNA methylation. However, how m6A methylation is involved in lupus nephritis (LN) is still unclear. This study aimed to determine the role of m6A RNA methylation and their association with the immune microenvironment in LN.MethodsIn total, 87 glomeruli (73 LN, 14 living healthy donors), 110 tubulointerstitium (95 LN, 15 living healthy donors), and 21 kidney whole tissue samples (14 LN, 7 controls) were included in our research to evaluate the expression levels of m6A regulators. CIBERSORT was used to assess the abundance of infiltrating immunocytes. The m6A regulator gene signature for LN was identified using LASSO-logistic regression and verified with external data. Consensus clustering algorithms were used for the unsupervised cluster analysis of m6A modification patterns in LN. Single-sample gene-set enrichment analysis and gene set variation analysis algorithms were employed to assess the activity of immune responses and other functional pathways. Weighted gene co-expression network analysis and protein-protein interaction networks were used to identify m6A methylation markers. Lastly, the Nephroseq V5 tool was used to analyze the correlation between m6A markers and renal function.ResultsWe found that the expression of m6A regulators was more significantly different in the glomeruli in LN compared with tubulointerstitium and whole kidney tissue. We established an m6A regulator signature, comprised of METTL3, WTAP, YTHDC2, YTHDF1, FMR1, and FTO, that can easily distinguish LN and healthy individuals. Two distinct m6A modification patterns based on 18 m6A regulators were determined, with significant differences in m6A regulator expression, immune microenvironment, biological functional pathways, and clinical characteristics. Activated NK cells, most immune responses, and HLA genes had strong correlations with m6A regulators. Seven m6A markers were identified and demonstrated a meaningful correlation with GFR, indicating that they are potential prognostic biomarkers.ConclusionThis study emphasized that m6A RNA methylation and the immune microenvironment are closely linked in LN. A better understanding of m6A modification patterns provide a basis for the development of novel therapeutic options for LN.

Project description:BackgroundFat percentage and distribution in pigs are associated with their productive efficiency and meat quality. Dietary branched-chain amino acids (BCAA) regulate fat metabolism in weanling piglets with unknown mechanism. It is reported that N6-methyl-adenosine (m6A) is involved in fat metabolism in mice. The current study was designed to investigate the relationship between dietary branched-chain amino acids and fat metabolism through N6-methyl-adenosine (m6A) in weanling piglets.MethodsA total of 18 healthy crossbred weaned piglets (Duroc × Landrace × Large White, 10.45 ± 0.41 kg) were divided into 3 treatments and were fed the low BCAA dose diet (L-BCAA), the normal dose BCAA diet (N-BCAA), or the high dose BCAA (H-BCAA) diet for 3 weeks.ResultsOur results show that compared with the N-BCAA group, the L-BCAA group had higher concentration of serum leptin (P < 0.05), while the H-BCAA group had lower concentration of serum adiponectin (P < 0.05). Fatty acid synthesis in pigs from the H-BCAA group was lower than those from the N-BCAA group with the down-regulation of lipogenic genes (ACACA, FASN, PPAR-r, SREBP-1c in ventral and dorsal fat, SREBP-1c in liver) and up-regulation of lipolysis genes (HSL, ATGL, CPT-1A, FABP4 in ventral fat, HSL in liver) (P < 0.05). Similarly, fatty acid synthesis in pigs from the L-BCAA group was also lower than those from the N-BCAA group with the decrease of lipogenic genes (ACACA in ventral, ACACA and FASN in dorsal fat, ACACA, FASN, SREBP-1c in liver) and the increase of lipolysis genes (ATGL, CPT-1A CD36, FABP4 in ventral fat and HSL, ATGL, CPT-1A in dorsal fat, CPT-1A) (P < 0.05). Feeding H-BCAA diet significantly reduced total m6A levels in ventral and dorsal fat and liver tissues (P < 0.05). The decrease of total m6A is associated with down-regulation of METTL3, METTL14 and FTO in dorsal fat and METTL3 and FTO in liver (P < 0.05). Decreased m6A modification of ACACA and FASN in ventral and dorsal adipose tissues was observed in pig fed with excessive BCAA.ConclusionThese results suggest that insufficient or excessive BCAA decreased the fat deposition by increasing lipolysis and deceasing lipogenesis in adipose and liver tissues. Dietary excessive BCAA might regulate the process of lipid metabolism partly through the m6A RNA methylation.

Dataset Information

Modification of STIM2 by m⁶A RNA methylation inhibits metastasis of cholangiocarcinoma.

Background

Methods

Results

Conclusions

Publications

Modification of STIM2 by m<sup>6</sup>A RNA methylation inhibits metastasis of cholangiocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Modification of STIM2 by m6A RNA methylation inhibits metastasis of cholangiocarcinoma.

Background

Methods

Results

Conclusions

Publications

Modification of STIM2 by m<sup>6</sup>A RNA methylation inhibits metastasis of cholangiocarcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Modification of STIM2 by m⁶A RNA methylation inhibits metastasis of cholangiocarcinoma.