Regulation of hsa_circ_0112136 by m6A demethylase FTO can enhance the malignancy of gastric cancer via the regulation of the PI3K/AKT/mTOR pathway.

A growing body of research highlights the role that N6-methyladenosine (m6A) modification and circular RNAs (circRNAs) play in gastric cancer (GC) cases. However, studies elucidating the function and mechanism of the recently discovered circRNA hsa_circ_0112136 in GC are limited. This study aimed to examine the pathophysiology of GC progression due to fat mass and obesity-associated protein (FTO)-mediated N6-methyladenosine (m6A) modification of hsa_circ_0112136. The hsa_circ_0112136 and FTO levels in the GC samples were analyzed using qRT-PCR. The Transwell invasion assay, wound healing assay, and CCK8 assays were employed to assess alterations in GC cell invasiveness, migration, and viability due to the aberrant regulation of hsa_circ_0112136 and FTO. Phosphorylated PI3K, AKT, and mTOR (the key proteins of the PI3K/AKT/mTOR pathway) were detected via western blotting after hsa_circ_0112136 suppression. A tumor transplantation mouse model was constructed to evaluate the suppression of hsa_circ_0112136's function in vivo. The correlation among hsa_circ_0112136 and FTO was identified using the MeRIP assay. Levels of hsa_circ_0112136 and FTO were evidently elevated in GC samples. Suppression of has_circ_0112136 reduced the viability, migration, and invasive ability of GC cells in vitro, as well as delayed tumor growth in vivo via suppression of the activation of the PI3K/AKT/mTOR pathway. FTO decreased hsa_circ_0112136 m6A levels and enhanced hsa_circ_0112136 expression. Furthermore, FTO upregulation enhanced GC cell invasion, migration, and survival, which was reversed by hsa_circ_0112136 suppression. Our study proposes that hsa_circ_0112136 functions as a tumor promoter, facilitating the malignant progression of GC through m6A modification (suppressed by FTO) and activating the PI3K/AKT/mTOR pathway. This suggests that targeting FTO-m6A-hsa_circ_0112136-PI3K/AKT/mTOR may be a novel approach for GC intervention.

Liu J ，Fang X 《-》

hsa_circ_0023409 Accelerates Gastric Cancer Cell Growth and Metastasis Through Regulating the IRS4/PI3K/AKT Pathway.

Li J ，Yang Y ，Xu D ，Cao L ... -  《-》

Upregulation of LncRNA WT1-AS Inhibits Tumor Growth and Promotes Autophagy in Gastric Cancer via Suppression of PI3K/Akt/mTOR Pathway.

Zhang X ，Jin M ，Yao X ，Liu J ，Yang Y ，Huang J ，Jin G ，Liu S ，Zhang B ... -  《-》

ZC3H13-induced the m6A modification of hsa_circ_0081723 promotes cervical cancer progression via AMPK/p53 pathway.

N6-methyladenosine (m6A) modification and circular RNAs (circRNAs) have been confirmed to participate in cervical cancer (CC) progression. However, the function of a novel circRNA, hsa_circ_0081723, has not yet been explored in CC. Therefore, this study aimed to investigate the potential role of hsa_circ_0081723 and its m6A modification in CC. The hsa_circ_0081723 and ZC3H13 expressions were examined by qRT-PCR in the CC tissues, and their prognostic significance was evaluated via Kaplan-Meier Plotter. The role of hsa_circ_0081723 in CC progression was checked by loss-of-function assays. The relative protein levels of AMPK/p53 pathway were determined by western blotting. The interactions of hsa_circ_0081723 and ZC3H13 were verified via MeRIP and RNA stability assays. The hsa_circ_0081723 expression was elevated in CC samples, and its higher levels indicated high histological grade, high FIGO stage, poor differentiation, and poor prognosis. Functionally, silencing hsa_circ_0081723 impaired the malignant behavior of CC cells and enhanced the protein levels of key molecules of the AMPK signaling pathway. Moreover, ZC3H13 was also elevated in CC samples and demonstrated a positive association with hsa_circ_0081723. The relative enrichment of hsa_circ_0081723 m6A and its stability were enhanced in ZC3H13 overexpressed CC cells. Mechanically, ZC3H13 overexpression partially reversed the antitumor effects caused by hsa_circ_0081723 knockdown in CC cells. This study innovatively demonstrates that ZC3H13-mediated m6A modification of hsa_circ_0081723 promotes CC progression by modulating AMPK/p53 pathway. Our findings may contribute to the understanding of the molecular mechanisms underlying CC and offer potential therapeutic targets for clinical treatment.

Wei Q ，Yang Y ，Li C ，Wang H ... -  《-》

Hsa_circ_0008667 promotes progression and improves the prognosis of gastric cancer by inhibiting miR-9-5p.

Gastric cancer (GC) is one of the most common gastrointestinal tumors characterized by aggressive development and poor prognosis. Circular RNAs (circRNAs) have been used as prognostic biomarkers and therapeutic targets in many cancers, including GC. Hsa_circ_0008667 is differentially expressed in GC; however, its function and clinical significance remained unelucidated. Therefore, this study aimed to investigate the role and significance of hsa_circ_0008667 in GC and its potential as a biomarker and therapeutic target of GC. Through quantitative reverse-transcription real-time PCR, hsa_circ_0008667 expression in GC tissues and cells were analyzed, followed by statistical analyses to assess the clinical significance. Cell Counting Kit-8 and Transwell assays were performed to examine the effects of hsa_circ_0008667 silencing on GC cell growth and metastasis. Additionally, correlation analysis was performed to assess the relationship between hsa_circ_0008667 and miR-9-5p, which was further validated through luciferase reporter assay. Hsa_circ_0008667 was considerably upregulated and tightly correlated with lymph node metastasis and the tumor-node-metastasis stage, which was predictive of poor prognosis in patients with GC. Hsa_circ_0008667 silencing suppressed GC cell proliferation, migration, and invasion. Furthermore, hsa_circ_0008667 negatively regulated miR-9-5p expression. MiR-9-5p downregulation enhanced GC malignancy and reversed hsa_circ_0008667 knockdown-mediated GC suppression. The findings of this study suggest hsa_circ_0008667 to be a prognostic biomarker and tumor promoter of GC via miR-9-5p modulation.

Ding W ，Li Z ，Liu X ，Wang J ，Wang J ，Jiang G ，Yu H ，Wang T ... -  《-》