Circ‐EIF3I facilitates proliferation, migration, and invasion of lung cancer via regulating the activity of Wnt/β‐catenin pathway through the miR‐1253/NOVA2 axis

Abstract

Many studies have shown that circular RNA (circRNA) is an important regulator mediating the malignant progression of cancer. However, the role and mechanism of circ-EIF3I in lung cancer (LC) development are still unclear. A total 36 paired LC tumor tissues and adjacent normal tissues were enrolled. The expression of circ-EIF3I, microRNA (miR)-1253, and neuro-oncological ventral antigen 2 (NOVA2) was measured by quantitative real-time PCR. The proliferation, apoptosis, migration, and invasion of LC cells were determined by MTT assay, colony formation assay, flow cytometry, and transwell assay. Dual-luciferase reporter assay was performed to verify the interaction between miR-1253 and circ-EIF3I or NOVA2. The protein levels of NOVA2 and Wnt/β-catenin pathway-related markers were detected by western blot analysis. Xenograft tumor was constructed to explore the function of circ-EIF3I on LC tumor growth. Circ-EIF3I was upregulated in LC tumor tissues and cells. Silenced circ-EIF3I could suppress the proliferation, migration, invasion, and enhance the apoptosis of LC cells in vitro, as well as reduce LC tumor growth in vivo. Circ-EIF3I could sponge miR-1253, and miR-1253 inhibitor overturned the regulation of circ-EIF3I knockdown on LC cell progression. NOVA2 was confirmed to be a target of miR-1253, which could reverse the inhibitory effects of miR-1253 on LC cell progression. Further experiments showed that circ-EIF3I regulated NOVA2 expression by sponging miR-1253. In addition, circ-EIF3I silencing could inhibit the activity of Wnt/β-catenin pathway via regulating the miR-1253/NOVA2 axis. Circ-EIF3I might function as an oncogene in LC, which promoted LC progression by the miR-1253/ NOVA2/Wnt/β-catenin network.

YY1/circCTNNB1/miR-186-5p/YY1 positive loop aggravates lung cancer progression through the Wnt pathway

“…lncRNA PKMYT1AR activates the Wnt pathway in non-small cell lung cancer to facilitate cancer stem cell maintenance [ 24 ]. CircEIF3I affects the Wnt/β-catenin pathway to strengthen cell proliferation and invasion by targeting the miR-1253/NOVA2 axis in lung cancer [ 25 ]. Cigarette smoking strengthens the Wnt/β-catenin pathway to stimulate tumorigenesis in lung cancer [ 26 ].…”

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

“…The protein level of β-catenin in NSCLC cells is upregulated by LINC00514 [ 109 ], lncRNA ITGB1-DT [ 110 ], lncRNA UPLA1 [ 21 ], RNASEH1-AS1 [ 111 ], circEIF3I [ 112 ], circZSWIM4 [ 113 ], KDM2B [ 114 ], SETD1A [ 115 ], EHD1 [ 116 ], TRIM27 [ 117 ] and HORMAD1 [ 118 ] (Table 2 ). Of them, lncRNA ITGB1-DT facilitates LUAD progression through forming a positive feedback loop with ITGB1/Wnt/β-Catenin/MYC axis [ 110 ].…”

“…RNASEH1-AS1 exacerbated the progression of NSCLC by regulating the miR-516a-5p/FOXK1/β-catenin axis [ 111 ]. Circ-EIF3I could sponge miR-1253, which targets NOVA2 and promotes Wnt/β-catenin signaling [ 112 ]. CircZSWIM4 promotes the development of LUAD by targeting miR-370-3p and miR-873-5p to regulate FOXM1/β-catenin axis [ 113 ].…”

Deciphering the Enigmatic Influence: Non-Coding RNAs Orchestrating Wnt/β-Catenin Signaling Pathway in Tumor Progression

“…Several other ncRNAs have also been found to be intimately involved in the initiation and progression with LC [ 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. For example, circEIF3I positively regulates NOVA2 expression by sequestering miR-1253 and further modulates the activity of the Wnt/β-catenin signaling pathway, promoting LC progression.…”