Key result
Elevated MNX1-AS1 expression in gallbladder cancer is strongly associated with reduced patient survival and stimulates tumor proliferation and metastasis via a positive feedback loop.
MNX1-AS1 facilitates tumorigenesis and metastasis in gallbladder cancer via a positive feedback loop with the USP16/IGF2BP3 axis and Hippo pathway.
Elevated MNX1-AS1 may aid GBC diagnosis; leaves open its mechanistic role and therapeutic targeting pending validation.
The long non-coding RNAs (lncRNAs) have been implicated in multiple human cancers, which may offer great potential as putative targets for cancer diagnosis and treatment. However, the roles of most lncRNAs in gallbladder cancer (GBC) remain poorly understood. The objective of this research involves investigating the clinical implications and underlying mechanism of lncRNA motor neuron and pancreas homeobo×1 antisense RNA 1 (MNX1-AS1) in GBC. This study shows that MNX1-AS1 expression is elevated in the tissues of GBC patients, and is strongly associated with reduced patient survival. Functionally, MNX1-AS1 significantly stimulates the proliferation and metastasis of GBC cells in vitro and in vivo. Mechanistically, MNX1-AS1 is transcriptionally activated by TEA domain family member 4 (TEAD4), and suppresses insulin-like growing factor 2 mRNA-binding protein 3 (IGF2BP3) degradation by recruiting ubiquitin specific peptidase 16 (USP16). Furthermore, MNX1-AS1/IGF2BP3 axis inhibits the Hippo signaling pathway and subsequently activates TEAD4, thereby forming a positive feedback loop. According to our results, MNX1-AS1 facilitates tumorigenesis, progression and metastasis of GBC through a MNX1-AS1/IGF2BP3/Hippo pathway positive feedback loop, which could be both diagnostically and therapeutically helpful in GBC.
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Liu et al. (2022) studied Gallbladder cancer. Elevated lncRNA MNX1-AS1 expression was evaluated on Patient survival, tumor proliferation, and metastasis. Elevated MNX1-AS1 expression in gallbladder cancer is strongly associated with reduced patient survival and stimulates tumor proliferation and metastasis via a positive feedback loop.
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