American Association for Cancer Research
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00085472can190799-sup-218596_3_supp_5627162_pnnpyh.pdf (1.86 MB)

Supplementary Figures S1-S11 from Long Noncoding RNA FAM225A Promotes Nasopharyngeal Carcinoma Tumorigenesis and Metastasis by Acting as ceRNA to Sponge miR-590-3p/miR-1275 and Upregulate ITGB3

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posted on 2023-03-31, 02:43 authored by Zi-Qi Zheng, Zhi-Xuan Li, Guan-Qun Zhou, Li Lin, Lu-Lu Zhang, Jia-Wei Lv, Xiao-Dan Huang, Rui-Qi Liu, FoPing Chen, Xiao-Jun He, Jia Kou, Jian Zhang, Xin Wen, Ying-Qin Li, Jun Ma, Na Liu, Ying Sun

Supplementary Figure S1. FAM225A is overexpressed in NPC and other tumor types. Supplementary Figure S2. Silencing METTL3 resulted in the decreased m6A level of total RNA. Supplementary Figure S3. FAM225A promotes NPC cell proliferation, migration and invasion in vitro. Supplementary Figure S4. FISH assay showed that FAM225A was mainly located in cytoplasmic. Supplementary Figure S5. FAM225A acts as a ceRNA for miR-590-3p and miR-1275. Supplementary Figure S6. The expression of FAM225A is negatively correlated with miR-590-3p and miR-1275 expression. Supplementary Figure S7. Silencing of miR-590-3p and miR-1275 endows NP69 and N2Tert cells with carcinogenicity in vitro. Supplementary Figure S8. miR-590-3p/miR-1275 are responsible for FAM225A-mediated proliferation, migration and invasion. Supplementary Figure S9. Correlation between FAM225A and ITGB3 expression in 12 other cancer types from the TCGA database. Supplementary Figure S10. FAM225A promotes NPC cell metastasis in vivo. Supplementary Figure S11. ITGB3 is responsible for FAM225A-meidated tumorigenesis and metastasis in vivo.

Funding

National Natural Science Foundation of China

Natural Science Foundation of Guangdong Province

National Key R&D Program of China

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ARTICLE 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 β3 (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. 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.

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