LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond

Huang, Wanxu; Li, Hua; Yu, Qingsong; Xiao, Wei; Wang, Dan Ohtan

doi:10.1186/s13046-022-02319-z

Cited by 99 publications

(67 citation statements)

References 142 publications

(125 reference statements)

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“…lncRNAs work mainly through the following four ways: first, induction, lncRNAs can bind to a specific miRNA, which can indirectly regulate the target gene; second, lncRNAs can act as a signal molecule on the pathway and regulate the upstream- and downstream-related genes of its target gene [ 31 , 32 ]. Third, by guiding the relevant RNA-binding proteins, lncRNAs are able to mediate the target genes via cis- or trans-regulation to specific protein complex sites [ 33 , 34 ]. Fourth, scaffolds, lncRNAs can be used as a platform; on this platform, a variety of related molecular complexes can be combined together to enhance the information transmission and interaction between molecular complexes [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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Long noncoding RNAs (lncRNAs) stand as indispensable regulators of initiation and development in melanoma (melanoma). However, the action molecular mechanisms linked to melanoma remain unclear. In the current study, the findings revealed that AGAP2-AS1 was considerably greater in melanoma than in healthy tissues and that the level of AGAP2-AS1 in cancer tissue was significantly linked to the cancerous TNM stage of patients. Individuals with high AGAP2-AS1 had a considerably shorter survival duration than patients with low AGAP2-AS1, regardless of progression-free survival or overall survival. Functionally, downregulating the expression of AGAP2-AS1 can inhibit the growth of melanocytes. Compared with the control group, AGAP2-AS1 knockdown increased Erastin-mediated iron death in melanoma cells. However, iron death inhibitor FERSINT-1 restored this effect, while Erastin induced melanoma cell death. Besides, intracellular iron and Fe2+ levels increased after AGAP2-AS1 knockdown in melanoma cells treated with Erastin compared with the si-NC group. In addition, AGAP2-AS1 silencing resulted in a significant decrease in glutathione (GSH) content in Erastin-treated melanoma cells. The mechanistic results suggest AGAP2-AS1 increases SLC7A11 mRNA stability through the IGF2BP2 pathway. In this investigation, we discovered new activities for AGAP2-AS1 and firstly discovered its mechanistic basis in ferroptosis and melanoma formation that might help in the search for potential therapy options in melanoma.

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Section: Discussionmentioning

confidence: 99%

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

Huang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…Our microarray analysis suggested that RARB was significantly upregulated in cells with DLEU2 knockdown and the subsequent qMSP assay identified increased DNA methylation at the RARB promoter. As aforementioned, lncRNAs may recruit, sequester, or regulate expression of DNMTs to regulate DNA methylation in downstream genes [ 15 ]. A recent publication by Zhang et al ., for instance, reported that lncRNA LALC recruits DNMTs to LZTS1 promoter to suppress its expression, which facilitated liver metastasis of CRC [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…DLEU2 has been associated with the proliferation and invasiveness of CRC cells [ 13 ], yet the possible molecules involved remain largely unknown. Intriguingly, certain lncRNAs may serve as manipulators for DNA methylation by regulating specific DNA methyltransferases (DNMTs) or Ten-eleven translocation family of enzymes [ 14 , 15 ]. DNA methylation refers to the selective methylation of cytosine within a cytosine-phosphate-guanine (CpG) dinucleotide, thus forming 5-methylcytosine [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Deleted in lymphocytic leukemia 2 induces retinoic acid receptor beta promoter methylation and mitogen activated kinase-like protein activation to enhance viability and mobility of colorectal cancer cells

Shi

Chen

2022

Bioengineered

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Abnormal expression of long non-coding RNAs (lncRNAs) is frequently linked to the pathogenesis of colorectal cancer (CRC). This work explored the function of lncRNA deleted in lymphocytic leukemia 2 (DLEU2) in CRC and the epigenetic mechanism. Candidate oncogenes in CRC were predicted using a GSE146587 dataset. DLEU2 was highly expressed in CRC according to the bioinformatic analysis and its high expression was detected in CRC cells compared to the normal colon epithelial cells (FHC). Downregulation of DLEU2 in CRC SW480 and HT29 cells suppressed viability, migration, invasiveness, and resistance to apoptosis of cells. The mRNA microarray analysis was performed to explore the key molecules mediated by DLEU2. Retinoic acid receptor beta (RARB) expression was elevated in cells after DLEU2 downregulation. The promoter methylation of RARB was enhanced in CRC cells compared to normal FHC cells. DLEU2 induced promoter methylation of RARB to downregulate its expression. Further silencing of RARB restored proliferation and invasiveness of cells blocked by sh-DLEU2. Upregulation of DLEU2 activated the mitogen activated kinase-like protein (MAPK) signaling pathway to trigger CRC progression. In conclusion, this study demonstrates that DLEU2 enhances viability and mobility of CRC cells by inducing RARB promoter methylation and activating the MAPK signaling pathway.

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“…Long noncoding RNAs (lncRNAs) are non-coding single-stranded RNAs with more than 200 nucleotides and have been found playing important roles in many biological processes in recent years. 12,13 LncRNA-H19 was one of the earliest lncRNAs to be discovered and has been increasingly recognized for its abilities to participate in cell function regulation, transcription and post transcriptional modification. 14,15 Our prior studies demonstrated that lncRNA-H19 regulated cell proliferation and invasion of ectopic endometrium by targeting ITGB3 via modulating miR-124-3p, 16 and it has also been reported that lncRNAs can be regulated by estrogen, 17,18 but it remains unclear whether estrogen regulates the expression and functions of lncRNA-H19 to participate in the pathogenesis of endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estrogen Regulates the Expression and Function of lncRNA-H19 in Ectopic Endometrium

Liu¹,

Tang²,

Li³

et al. 2022

IJWH

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Background: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of endometriosis and can be regulated by estrogen. This study aimed to investigate the role of estrogen in regulating the expression and function of lncRNA-H19 in endometriosis. Methods: Endometrial stromal cells (ESCs) were isolated from ectopic, eutopic endometrium with endometriosis and control endometrium without endometriosis, and lncRNA-H19 expression was detected using real-time polymerase chain reaction (RT-PCR). Ectopic endometrial stromal cells (ecESCs) were treated with 17β-estradiol at 10 −8 mol/L for 0, 12, 24 and 48 hours, and lncRNA-H19 expressions of cells were evaluated using RT-PCR. After ecESCs were treated with 17β-estradiol for 48 hours, lncRNA-H19 expression was knocked down and cell proliferative and invasive abilities were compared. Results: The expression of lncRNA-H19 in ecESCs was significantly higher than that in eutopic endometrial stromal cells (euESCs) and control ESCs. After treated with 17β-estradiol, ecESCshadupregulatedlncRNA-H19 expression with time-dependent manner. Cell proliferation and invasion increased when estrogen upregulated lncRNA-H19 expression in ecESCs, however, cell proliferation restored and cell invasion did not change when lncRNA-H19 was knocked down in ecESCs. Conclusion:The expression and function of lncRNA-H19 was regulated by estrogen in ecESCs, which probably contributed to the pathogenesis of endometriosis.

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LncRNA-mediated DNA methylation: an emerging mechanism in cancer and beyond

Cited by 99 publications

References 142 publications

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma

Deleted in lymphocytic leukemia 2 induces retinoic acid receptor beta promoter methylation and mitogen activated kinase-like protein activation to enhance viability and mobility of colorectal cancer cells

Estrogen Regulates the Expression and Function of lncRNA-H19 in Ectopic Endometrium

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