CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex.
CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex.
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CircARID1A与胃癌中的IGF2BP3结合，通过形成circARID1A-IGF2BP3-SLC7A5 RNA-蛋白质三元复合物促进癌症增殖
DOI：
10.1186/s13046-022-02466-3
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发表时间：
2022-08-19
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
Gastric cancer (GC) is one of the most common malignant tumors in China. Circular RNAs (circRNAs) are novel non-coding RNAs with important regulatory roles in cancer progression. IGF2BP3 has been found to play oncogenic roles in various cancers including GC, while the exact mechanism of IGF2BP3 is largely unknown. The expression of IGF2BP3 in GC was evaluated by Western Blot and bioinformatics analysis. CircRNA expression profiles were screened via IGF2BP3 RIP-seq in GC. Sanger sequencing, RNase R digestion, nucleo-plasmic separation and RNA-FISH assays were used to detect the existence and expression of circARID1A. RNA ISH assay was employed to test the expression of circARID1A in paraffin-embedded GC tissues. Moreover, the function of circARID1A on cellular proliferation was assessed by CCK-8, plate colony formation, EdU assays and GC xenograft mouse model in vivo. Furthermore, the location or binding of circARID1A, IGF2BP3 protein and SLC7A5 in GC was evaluated by RNA-FISH/IF or RNA pull-down assays. We identified a novel circRNA, circARID1A, that can bind to IGF2BP3 protein. CircARID1A was significantly upregulated in GC tissues compared with noncancerous tissues and positively correlated with tumor length, tumor volume, and TNM stage. CircARID1A knockdown inhibited the proliferation of GC cells in vitro and in vivo and circARID1A played an important role in the oncogenic function of IGF2BP3. Mechanistically, circARID1A served as a scaffold to facilitate the interaction between IGF2BP3 and SLC7A5 mRNA, finally increasing SLC7A5 mRNA stability. Additionally, circARID1A was able to directly bind SLC7A5 mRNA through complementary base-pairing and then formed the circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex and promoted the proliferation of GC via regulating AKT/mTOR pathway. Altogether, our data suggest that circARID1A is involved in the function of IGF2BP3 and GC proliferation, and the circARID1A-IGF2BP3-SLC7A5 axis has the potential to serve as a novel therapeutic target for GC. The online version contains supplementary material available at 10.1186/s13046-022-02466-3.
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影响因子：
4.6
作者：
Jigjidkhorloo N;Kanekura K;Matsubayashi J;Akahane D;Fujita K;Oikawa K;Kurata A;Takanashi M;Endou H;Nagao T;Gotoh A;Norov O;Kuroda M
通讯作者：
Kuroda M
IMP3蛋白是临床II期直肠癌的独立预后因素。
影响因子：
4.6
作者：
Bevanda Glibo D;Bevanda D;Vukojević K;Tomić S
通讯作者：
Tomić S
影响因子：
11.5
作者：
Mancarella, Caterina;Pasello, Michela;Scotlandi, Katia
通讯作者：
Scotlandi, Katia
DOI：
10.1016/j.omtn.2020.11.012
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Liang Y;Wang H;Chen B;Mao Q;Xia W;Zhang T;Song X;Zhang Z;Xu L;Dong G;Jiang F
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Jiang F
影响因子：
64.8
作者：
Gong, Chenguang;Maquat, Lynne E.
通讯作者：
Maquat, Lynne E.