LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM.
Feifei ZhangHui WangJiang YuXueqing YaoShibin YangWeidong LiLijun XuLiang ZhaoPublished in: Molecular cancer (2021)
De novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.
Keyphrases
- long noncoding rna
- cell death
- gas chromatography
- induced apoptosis
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- binding protein
- transcription factor
- genome wide
- poor prognosis
- locally advanced
- protein protein
- radiation therapy
- long non coding rna
- amino acid
- squamous cell carcinoma
- copy number
- climate change
- rectal cancer
- dna methylation