RETRACTED: MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3

Huang, Shaohong; Luo, Shaoning; Gong, Chulian; Liang, Limin; Xiao, Yi; Li, Mingan; He, Jing

doi:10.1016/j.omtn.2021.02.020

Cited by 23 publications

(18 citation statements)

References 34 publications

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“…METTL3 can regulate MALAT1 stabilization through m6A modification, and it activates NF-κB activity to promote the malignant progression of glioma [ 36 ]. METTL3 increases miR-1246 levels through m6A modification, thereby promoting non-small-cell lung cancer progression [ 37 ]. Moreover, METTL3 regulates the m6A modification of SPHK2 to promote the progression of gastric cancer [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Pan

Liu

Xiao

et al. 2022

J Exp Clin Cancer Res

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Background Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. Methods Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. Results M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain–containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. Conclusions M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A–CRB3–Hippo pathway.

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Section: Discussionmentioning

confidence: 99%

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Pan

Liu

Xiao

et al. 2022

J Exp Clin Cancer Res

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“…METTL3 could regulate MALAT1 stabilization via m6A modi cation, and activate NF-κB activity to promote the malignant progression of glioma [36]. METTL3 increased miR-1246 level via the m6A modi cation, thus to promote non-small cell lung cancer progression [37]. Moreover, METTL3 regulated m6A modi cation of SPHK2 to contribute the progression of gastric cancer [38].…”

Section: Discussionmentioning

confidence: 99%

METTL3 Facilitates Colorectal Carcinoma Progression via Regulating m6A-CRB3-Hippo Axis

Liu¹,

Xiao²,

Pan³

et al. 2021

Preprint

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Background Colorectal carcinoma (CRC) is the third most common cancer and the second most common cause of cancer-related death worldwide. RNA N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play an important role in cancer. However, the roles of m6A and METTL3 in CRC progression are still elusive. Methods Adenoma and CRC samples were applied to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate their associations with survival of CRC patients. The biological functions of METTL3 were investigated by CCK8, wound healing and transwell assays. M6A epitranscriptomic microarray, RNA stability and luciferase reporter assays were performed to explore the mechanism of METTL3 in CRC. Results m6A and METTL3 levels were significantly upregulated in both adenoma and CRC tissues, and the CRC patients with high m6A or METTL3 level had both shorter overall survival. METTL3 knockdown markedly inhibited the proliferation, migration and invasion of CRC cells. M6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown markedly inhibited the degradation of CRB3 mRNA to increase the CRB3 expression. In addition, CRB3 level was also markedly reduced in both adenoma and CRC tissues, and the CRC patients with high CRB3 level had higher overall survival and disease free survival. CRB3 knockdown significantly promoted the proliferation, migration and invasion of CRC cells. Finally, CRB3 knockdown inhibited Hippo pathway, and increased nuclear localization of YAP. Conclusions The m6A and METTL3 levels were significantly increased in both adenoma and CRC tissues. The CRC patients with high m6A or METTL3 levels had shorter overall survival. Mechanistically, METTL3 regulated the initiation and progression of CRC via regulating m6A-CRB3-Hippo pathway.

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“…Analogously to its impact on bladder carcinoma, METTL3 facilitated the pri-miR-1246 maturation process and paved the way for the enhanced metastasis of CRC cells via the MAPK signaling pathway (64). Analogously, METTL3 upregulated miR-1246 expression and contributed to NSCLC cell growth (65). Likewise, miR-25-3p maturation was impeded by m6A modification mediated by METTL3 in pancreatic ductal adenocarcinoma (16).…”

Section: M6a-mediated Processing Of Primary-mirnasmentioning

confidence: 99%

N6-Methyladenosine-Sculpted Regulatory Landscape of Noncoding RNA

et al. 2021

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The exploration of dynamic N6-methyladenosine (m6A) RNA modification in mammalian cells has attracted great interest in recent years. M6A modification plays pivotal roles in multiple biological and pathological processes, including cellular reprogramming, fertility, senescence, and tumorigenesis. In comparison with growing research unraveling the effects of m6A modifications on eukaryotic messenger RNAs, reports of the association between noncoding RNAs and m6A modification are relatively limited. Noncoding RNAs that undergo m6A modification are capable of regulating gene expression and also play an important role in epigenetic regulation. Moreover, the homeostasis of m6A modification can be affected by noncoding RNAs across a broad spectrum of biological activities. Importantly, fine-tuning and interaction between these processes are responsible for cell development, as well as the initiation and progression of the disease. Hence, in this review, we provide an account of recent developments, revealing biological interactions between noncoding RNAs and m6A modification, and discuss the potential clinical applications of interfering with m6A modification.

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RETRACTED: MTTL3 upregulates microRNA-1246 to promote occurrence and progression of NSCLC via targeting paternally expressed gene 3

Cited by 23 publications

References 34 publications

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

METTL3 Facilitates Colorectal Carcinoma Progression via Regulating m6A-CRB3-Hippo Axis

N6-Methyladenosine-Sculpted Regulatory Landscape of Noncoding RNA

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