Loss of ferrochelatase is protective against colon cancer cells: ferrochelatase a possible regulator of the long noncoding RNA H19

Objective To examine the role of the long noncoding RNA LINC01296 in colorectal carcinoma (CRC) and to explore the underlying mechanism. Methods We detected LINC01296 expression levels in a cohort of 51 paired CRC and normal tissues. We also assessed the effects of LINC01296 on cell proliferation and apoptosis in CRC cells in vitro, and measured its effect on tumor growth in an in vivo mouse model. We identified the potential downstream targets of LINC01296 and assessed its regulatory effects. Results Expression levels of LINC01296 were elevated in 37/51 CRC tissues compared with the corresponding normal tissues and were significantly associated with tumor stage, lymph node metastasis, and distant metastasis. Knockdown of LINC01296 using antisense oligonucleotides inhibited cell proliferation and promoted apoptosis of colon cancer cells in vitro and inhibited tumor growth in vivo. Knockdown of LINC01296 also significantly increased the gene expression of p15 in colon cancer cells. LINC01296-specific suppression of p15 was validated by the interaction between enhancer of zeste homolog 2 and LINC01296. Conclusion Overexpression of LINC01296 suppressed the expression of p15 leading to CRC carcinogenesis. These findings may provide the basis for novel future CRC-targeted therapies.

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Long Noncoding RNA LINC01207 Promotes Colon Cancer Cell Proliferation and Invasion by Regulating miR-3125/TRIM22 Axis

BioMed Research International ◽

10.1155/2020/1216325 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ronghong Liu ◽

Wenzeng Zhao ◽

Haigang Wang ◽

Jianbing Wang

Keyword(s):

Colon Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Noncoding Rna ◽

Colon Cancer Cell ◽

Migration And Invasion ◽

Cancer Cell Proliferation ◽

Colon Cancer Cells ◽

Proliferation And Invasion

Increasing study has validated that long noncoding RNAs (lncRNAs) are involved in the growth and metastasis of colon cancer. LINC01207 has been reported to play vital roles in certain types of cancer, while the precise function of LINC01207 in the progression of colon cancer remains unclear. The objective of this study was to investigate the effect of LINC01207 on the growth and metastasis of colon cancer cells and to explore the underlying mechanism. We found that the expression of LINC01207 was significantly upregulated in colon adenocarcinoma tissues compared with normal tissues by the GEPIA database. Notably, silencing of LINC01207 significantly suppressed the proliferation, migration, and invasion abilities of SW480 and HT-29 cells. Mechanistically, our data demonstrated that LINC01207 could sponge miR-3125 in colon cancer cells. Moreover, miR-3125 could directly target TRIM22 and negatively regulate its expression. Rescue assays revealed that miR-3125 inhibitor or TRIM22 overexpression significantly reversed the repressive role of LINC01207 knockdown in colon cancer cell proliferation and invasion. In conclusion, LINC01207 exerts an oncogenic role in the progression of colon cancer by absorbing miR-3125 to modulating TRIM22 expression.

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NSUN2-Mediated Splice Site m5C Methylation Modification Promotes the Progression of Colon Cancer Through Modulating the Discrepant Cleavage of tRNA-Arg

10.21203/rs.3.rs-786758/v1 ◽

2021 ◽

Author(s):

Na Luan ◽

Yanjing Cao ◽

Jianguo Sun ◽

Jiayi Mu ◽

Yali Mu ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Noncoding Rna ◽

Cancer Metastasis ◽

Tumour Progression ◽

Colon Cancer Cells ◽

Rna Methylation ◽

Tumour Metastasis ◽

Colon Cancer Metastasis

Abstract Background: Hypoxia is a key driving factor for the tumour microenvironment restructuring, which leading to the variation of gene expression profiling in cancer cells. Increasing evidence reveals the initial action of hypoxia in the epitranscriptomics including RNA methylation. The role of tRNA-derived fragments (tRFs) in regulating tumour metastasis potential has attracted attention. Methods: The expression of tRFs in colon cancer cells under hypoxia were evaluated based on full-transcript sequencing and bioinformatics analysis and their effects on colon cancer metastasis were detected by transwell assays. The role of C34 was verified by introducing mutation and artificial m5C modification. The effects of NSUN2 on the biological characteristics of colon cancer cells were investigated on the basis of gain-of-function and loss-of function analyses. Lung metastasis model further uncovered the roles of NSUN2 and key tRF in tumour progression. Assays of RNA immunoprecipitation-qPCR (RIP-qPCR) were performed to identify that NSUN2 is a key methyltransferase for cysteine modification at C34 of tRNA-Arg.Results: The present study verified the up-expression of tRF (tRF-20-MEJB5Y13) and down-expression of tRFs (tRF-20-M0NK5Y93 and tRF-21-3OPP6N7KE) in colon cancer cells under hypoxia, and all of them were derived from different tRNA-Arg. Contradictory effects of these three tRNA-Arg-derived tRFs on metastatic potential of colon cancer were demonstrated in this study. The sequence differences and the key nucleotide bases of tRNA with the methylation modification potential among the source tRNAs were analysed. Notably, our data identified C34 of tRNA-Arg as a key site that may play an important role in hypoxia-mediated tRNA-Arg discrepant cleavage. We further investigated that NSUN2 mediated specific site methylation of tRNA-Arg at C34, thereby protecting tRNA from cleavage by endonuclease and subsequently promoting the colon cancer metastasis both in vitro and in vivo. Conclusion: The present study elaborates on the precise regulatory mechanism of m5C methylation and the role in the selective cleavage of tRNA from the perspective of noncoding RNA methylation epitranscriptomics, providing a novel insight into the molecular basis of selective expression of tRFs in colon cancer under hypoxia.

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