Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9

Liang, Lu; Xu, Wenyan; Shen, Ao; Cen, Huiyu; Chen, Zhijun; Tan, Lin; Zhang, Ling-min; Fu, Jijun; Qin, Aiping; Lei, Xueping; Li, Song-pei; Qin, Yuyan; Huang, Jionghua; Yu, Xiyong

doi:10.1038/s41401-022-00893-8

Cited by 18 publications

(20 citation statements)

References 42 publications

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“…MiR-30c has also recently been considered as a suppressor of bone gamma-carboxyglutamate protein ( BGLAP ) in osteogenesis ( 50 ). Target DEGs of miR-30c in our analysis were mostly related to the anti-apoptosis of abnormal tumor cells, including MAP3K9 in lung cancer ( 46 ), ST6GALNAC5 in prostate cancer ( 51 ), CSRNP3 in clear renal cell carcinoma ( 52 ), ZNF703 in breast tumors ( 53 ), and CLSPN in brain tumors ( 54 ). Thus, upregulation of hsa_circ_0102564 might help reveal the downstream mechanism involved in the abnormal maturation and proliferation of chondrocytes in OA.…”

Section: Discussionmentioning

confidence: 93%

“…However, the functions of hsa-miR-3202, hsa-miR-4516, and hsa-miR-4476 in OA have not been investigated. According to previous studies in other fields, miR-3202 can promote endothelial cell apoptosis through FAIM ( 45 ); miR-4516 inhibits liver cancer cell proliferation and progression through SOX5 ( 46 ); miR-4476 could promote glioma progression through APC/β-catenin in the Wnt pathway ( 47 ). From the perspective of regulated DEGs, CCND1 was one of DEGs regulated by miR-3202, according to our analysis.…”

Section: Discussionmentioning

confidence: 98%

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Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

et al. 2023

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Osteoarthritis (OA) is a common orthopedic degenerative disease, leading to high disability in activities of daily living. There remains an urgent need to identify the underlying mechanisms and identify new therapeutic targets in OA diagnosis and treatment. Circular RNAs (circRNAs) play a role in the development of multiple diseases. Many studies have reported that circRNAs regulate microRNAs (miRNAs) through an endogenous competitive mechanism. However, it remains unclear if an interplay between circRNAs, miRNAs, and target genes plays a deeper regulatory role in OA. Four datasets were downloaded from the GEO database, and differentially expressed circRNAs (DECs), differentially expressed miRNAs (DEMs), and differentially expressed genes (DEGs) were identified. Functional annotation and pathway enrichment analysis of DEGs and DECs were carried out to determine the main associated mechanism in OA. A protein–protein network (PPI) was constructed to analyze the function of, and to screen out, hub DEGs in OA. Based on the artificial intelligence prediction of protein crystal structures of two hub DEGs, TOP2A and PLK1, digitoxin and oxytetracycline were found to have the strongest affinity, respectively, with molecular docking. Subsequently, overlapping DEMs and miRNAs targeted by DECs obtained target DEMs (DETMs). Intersection of DEGs and genes targeted by DEMs obtained target DEGs (DETGs). Thus, a circRNA–miRNA–mRNA regulatory network was constructed from 16 circRNAs, 32 miRNAs, and 97 mRNAs. Three hub DECs have the largest number of regulated miRNAs and were verified through in vitro experiments. In addition, the expression level of 16 DECs was validated by RT-PCR. In conclusion, we constructed a circRNA–miRNA–mRNA regulatory network in OA and three new hub DECs, hsa_circ_0027914, hsa_circ_0101125, and hsa_circ_0102564, were identified as novel biomarkers for OA.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

et al. 2023

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“…Mitogen-activated protein kinase kinase kinase 9 (MAP3K9), a member of serine/threonine protein kinases, acts as an oncoprotein as well as a target of mIR-7, miR-148a-3p or miR-125b-5p in several cancers [48][49][50]. We herein identi ed MAP3K9 as a direct target of miR-186-3p, and METTL14 OE decreased MAP3K9 expression levels, but circUGGT2 OE promoted its expression and attenuated METTL14-induced MAP3K9 downregulation in GC cells.…”

Section: Discussionmentioning

confidence: 99%

METTL14-dependent m 6 A modification of circUGGT2 drives gastric cancer progression by sponging miR-186-3p and upregulating MAP3K9

Chen

Yang

Chen

et al. 2023

Preprint

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Background: N6-methyladenosine (m6A) RNA modification has been shown to act fundamental roles in cancer progression. However, the underlying mechanisms by which m6A modification of circRNAs contributes to gastric cancer (GC) remain unknown. Methods: METTL14-mediated m6A modification of circRNAs was identified by an m6A-circRNA epi-transcriptomic microarray and verified by methylated RNA immunoprecipitation (MeRIP) and m6A dot blot. Cell bio-behaviors were measured by molecular oncology experiments in vitro and in vivo. The mechanisms underlying gastric tumorigenesis were conducted by RIP, luciferase gene report, RT-qPCR. and Western blot analyses. The prognostic significance was analyzed by FISH and TCGA dataset. Results: We found that hsa_circ_0030632 (circUGGT2) was a predominant m6A target of METTL14, and METTL14 knockdown (KD) reduced circUGGT2 m6A levels but increased its mRNA levels. circUGGT2 KD impaired cell growth and metastasis in vitro and in vivo, but circUGGT2 overexpression prompted these effects. Furthermore, circUGGT2 was validated to sponge miR-186-3p and upregulate MAP3K9 and could abolish METTL14-caused miR-186-3p upregulation and MAP3K9 downregulation in GC cells. circUGGT2 negatively correlated with miR-186-3p expression and harbored a poor prognosis in patients with GC. Conclusion: Our findings unveil that METTL14-dependent m6A modification of circUGGT2 promotes GC progression by sponging miR-186-3p and upregulating MAP3K9.

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“…In our earlier research, we have demonstrated that the reduced expression of miR‐148a‐3p in lung adenocarcinoma is linked to the methylation of DNA in CpG islands located within the promoter regions of the miRNA 8 . Furthermore, we discovered that the target of miR‐148a‐3p is the mitogen activated protein (MAP) kinase kinase 9 (MAP3K9).…”

Section: Discussionmentioning

confidence: 99%

The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy

et al. 2023

MedComm

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Gene therapy has emerged as a potential approach for lung cancer therapy. However, the application of gene therapy is still limited by their properties, such as low specificity to the cancer cells, negatively charged groups, short systemic circulation time, and rapid degradation by nucleases. The progression of lung adenocarcinoma (LUAD) can be promoted through the methylation process of miR‐148a‐3p promoter, as confirmed by our previous research. In the current study, we are the first to design a mirrored Arg‐Gly‐Asp (RGD)‐modified cationic peptide (RD24) as a microRNA (miRNA) vehicle, which enabled to pack the miRNA (miR‐148a‐3p) efficiently and generate RD24/miR‐148a‐3p nanoparticles (RPRIN) by self‐assembling. RPRIN exhibited a high transfection efficiency in lung cancer cells via the conjugation between RGD and integrins on the surface of lung cancer cells. Furthermore, RD24 showed matrix metallopeptidase 2 (MMP2) responsiveness, which improved lung cancer cell inhibition induced by the miRNA intracellularly. In addition, RPRIN exhibits several advantages, such as prolonged circulation duration, reduced toxicity, and immune escape. Experiments conducted both in vitro and in vivo revealed that RPRIN effectively suppressed the growth and progression of lung cancer. Thus, the mirrored RGD‐modified cationic peptide showed great potential in transducing miRNA for lung cancer therapy.

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Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9

Cited by 18 publications

References 42 publications

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

METTL14-dependent m 6 A modification of circUGGT2 drives gastric cancer progression by sponging miR-186-3p and upregulating MAP3K9

The mirrored cationic peptide as miRNA vehicle for efficient lung cancer therapy

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