Long Noncoding RNA FAM225A Promotes Nasopharyngeal Carcinoma Tumorigenesis and Metastasis by Acting as ceRNA to Sponge miR-590-3p/miR-1275 and Upregulate ITGB3

Abstract

Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which, FAM225A was one of the most upregulated lncRNAs in NPC. FAM225A significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within FAM225A and enhanced its RNA stability. FAM225A functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically, FAM225A functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target integrin b3 (ITGB3), and the activation of FAK/PI3K/Akt signaling to promote NPC cell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which FAM225A modulates ITGB3 expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC. Significance: These findings demonstrate the clinical significance of the lncRNA FAM225A in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

“…Recently, Wu et al demonstrated that m 6 A modification upregulates lncRNA RP11 by increasing its nuclear accumulation [27]. m 6 A was suggested to be highly enriched on lncRNA FAM225A and can increase its RNA stability [26]. Herein, we revealed that m 6 A methylation was enriched within LINC00958 in HCC cells using both in silico data and m 6 A RIP experiment.…”

“…Recent advancements in tumor epigenetic regulation have shed light on the involvement of m 6 A modification in lncRNA [26,27]. We then wondered whether m 6 A was associated with LINC00958 upregulation in HCC.…”

The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

“…Studies have shown that one-third of the human genome can be regulated by miRNAs [55], which play an important regulatory role in cancers and metabolic diseases. Most miRNAs in the ceRNA network have been found to be closely related Journal of Diabetes Research to cancers [56][57][58][59]. In addition, Rohm et al [60] found that the expression of hsa-let-7d-5p was increased in the experimental group compared with the undifferentiated control group during adipogenesis.…”

ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma

“…Additionally, abnormal m 6 A modification contributes to the dysregulation of lncRNAs in human cancers. For example, m 6 A was highly enriched within lncRNA FAM225A and enhanced its RNA stability, resulting in nasopharyngeal carcinogenesis and metastasis [11]. m 6 A methylation was involved in the upregulation of lncRNA RP11 by increasing its nuclear accumulation in colorectal cancer cells [12].…”