METTL3/YTHDF1 m6A axis promotes tumorigenesis by enhancing DDR2 expression in ovarian cancer

Zhi, Duo; Zhou, Kun; Liu, Shuang; Yu, Wen; Dong, Mei; Yan, Caichuan

doi:10.1016/j.prp.2023.155047

Cited by 2 publications

(1 citation statement)

References 19 publications

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“…Mechanistic study shows PLAA promotes METTL3 degradation, leading to destabilization of TRPC3 which regulate intracellular calcium flux to inhibit metastasis in OC ( 103 ). The silencing of METTL3/YTHDF1 inhibit OC progression and mechanistic study reveals that METTL3/YTHDF1 axis enhanced the expression of the tumor-promoting DDR2 to foster the progression of OC ( 75 ). METTL3 is also reported to induce epithelial to mesenchymal transition (EMT) by enhancing AXL expression ( 76 ).…”

Section: M6a Rna Modifications Role In Modulating Oc Progressionmentioning

confidence: 99%

Emerging role of m6A modification in ovarian cancer: progression, drug resistance, and therapeutic prospects

Alam,

Giri

2024

Front. Oncol.

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Ovarian Cancer (OC) ranks as a prominent contributor to mortality among female reproductive system associated cancers, particularly the prevalent subtype epithelial Ovarian Cancer (EOC). Despite advancements in treatment modalities, the prognosis for OC patients remains grim due to limitation of current therapeutic methodology such as high cytotoxicity of chemotherapeutic agents and tumor relapse making existing chemotherapy ineffective. Recognizing the limitations of a broad-spectrum approach to treating OC, a shift toward targeted therapies aligning with unique molecular features is imperative. This shift stems from an incomplete understanding of OC’s origin, distinguishing it from extensively researched malignancies such as cervical or colon cancer. At the molecular level, postsynthetic modifications—DNA, RNA, and protein—shape transcriptional, posttranscriptional, and posttranslational processes. Posttranscriptional regulatory mechanisms, including RNA modifications are termed epitranscriptomic and play critical roles in this process. For more than five decades, 100+ RNA post-synthetic modifications, notably N6-methyladenosine (m6A), most prevalent RNA modification in mammals, dynamically regulate messenger RNA (mRNA), and non-coding RNA (ncRNA) life orchestrated via writers, erasers, and readers. The disruption of m6A modifications are found in several cancers, including OC, underscores pivotal role of m6A. This review focused on m6A modifications in coding and non-coding RNAs, emphasizing their role as prognostic markers in OC and their impact on development, migration, invasion, and drug resistance. Additionally, RNA-modified regulators have been explored as potential molecular and therapeutic targets, offering an innovative approach to combatting this challenging malignancy.

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Section: M6a Rna Modifications Role In Modulating Oc Progressionmentioning

confidence: 99%

Emerging role of m6A modification in ovarian cancer: progression, drug resistance, and therapeutic prospects

Alam,

Giri

2024

Front. Oncol.

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Anticancer effects of Erzhimaoling decoction in high-grade serous ovarian cancer in vitro and in vivo

Yang,

Liu,

Zhang

et al. 2024

Eur J Med Res

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Background High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo. Materials and methods EZMLD-containing serum was prepared from Sprague–Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC50. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks. Results In vitro, EZMLD-containing serum had IC50 values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression. Conclusions EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.

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METTL3/YTHDF1 m6A axis promotes tumorigenesis by enhancing DDR2 expression in ovarian cancer

Cited by 2 publications

References 19 publications

Emerging role of m6A modification in ovarian cancer: progression, drug resistance, and therapeutic prospects

Emerging role of m6A modification in ovarian cancer: progression, drug resistance, and therapeutic prospects

Anticancer effects of Erzhimaoling decoction in high-grade serous ovarian cancer in vitro and in vivo

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