The Long Noncoding RNA MAGI1-IT1 Regulates the miR-302d-3p/IGF1 Axis to Control Gastric Cancer Cell Proliferation

Abstract

Background: MAGI1-IT1 is a long non-coding RNA (lncRNA) previously reported to regulate several cancer types, but its functional role in gastric cancer (GC) remains to be defined. This study therefore explored the mechanistic role played by MAGI1-IT1 in the regulation of GC cell proliferation. Methods: 120 pairs of GC patient tumor, paracancerous tissues, human GES-1 control cells and human AGS, MKN-74, MKN-45, and MGC-803 GC cell lines were used to detected MAGI1-IT1, miR-302d-3p, and IGF1 expression by a qPCR approach. An shRNA approach was used to knock down MGI1-IT1 in order to examine the effect of such treatment on GC cell proliferation, and rescue experiments were subsequently conducted. In addition, the functional role of MAGI1-IT1 in GC in vivo was evaluated with a xenograft model system. P < 0.05 was the significance threshold. Results: Elevated MAGI1-IT1 expression was detected in GC cell lines and tissues, and was linked to poorer patient overall survival. Knocking down this lncRNA disrupted GC cell proliferation in vitro and in vivo, and miR-302d-3p was identified as a MAGI1-IT1 target. Notably, miR-302d-3p inhibition partially reversed the impact of MAGI1-IT1 knockdown on GC cell proliferation. IGF1 was subsequently identified as a miR-302d-3p target gene that was upregulated by MAGI1-IT1 through miR-302d-3p. Conclusion: Overall, these results indicated that MAGI1-IT1 controlled GC cell proliferation by modulating the miR-302d-3p/IGF1 axis, suggesting that this may be a viable treatment target in those with GC.

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“…Ning et al found that DSCAM-AS1 can accelerate cell value-addition and migration in osteosarcoma through GPRC5A signaling ( Ning and Bai, 2021 ). Wang et al found that MAGI1-IT1 has a regulatory role in controlling the value-addition of gastric cancer ( Wang et al, 2021 ). Sun et al found that LINC01133 also has a regulatory effect on the value-added of gastric cancer ( Sun et al, 2022 ).…”

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“…miR-144-3p is associated with the progression of several cancers, inhibiting cervical cancer [104], gastric cancer [105], and non-small-cell lung cancer (NSCLC) [106] in terms of proliferation, invasion, and migration. The other three miRNAs are associated with promoting tumor proliferation [107], migration [108], and drug resistance [109]. The downregulation of their expression after radiotherapy may play a role in blocking tumor invasion.…”

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“…Mechanistically, MAGI1-IT1 sequesters miR-302d-3p enabling accumulation of its target insulin-like growth factor 1 (IGF1). Knock-down of the lncRNA in the human gastric cancer AGS and MGC-803 cell lines decreases proliferation in vitro and tumor growth in nude mice [ 207 ].…”