Elucidating the pro-tumor role of LncRNA CROCCP2 in glioma via the miR-5584-5p/HOXD11/autophagy pathway

Glioma is the most common primary malignant tumor of the central nervous system, characterized by high invasiveness and a high recurrence rate. The clinical therapeutic efficacy remains limited, necessitating the exploration of novel molecular mechanisms and therapeutic targets. Long non-coding RNAs (lncRNAs), as key epigenetic regulators in tumor progression, can influence tumorigenesis and development through lncRNA–miRNA–mRNA regulatory axes. Here, we reveal the critical role of the lncRNA CROCCP2/miR-5584-5p/HOXD11 axis in glioma. LncRNA CROCCP2 was significantly upregulated in glioma tissues and cell lines, markedly promoting the proliferation, migration, and invasion of glioma cells. Mechanistically, LncRNACROCCP2 acts as a competing endogenous RNA to sponge miR-5584-5p, thereby relieving its suppression of the target gene HOXD11, leading to HOXD11 upregulation. HOXD11 further promotes glioma progression by inhibiting autophagy, as evidenced by the downregulation of LC3B-II and Beclin1. Knockdown of either lncRNA CROCCP2 or HOXD11 activated autophagy and suppressed malignant behaviors. In addition, HOXD11 silencing markedly inhibited subcutaneous and intracranial tumor growth in nude mice, whereas HOXD11 overexpression partially reversed the inhibitory effects induced by lncRNACROCCP2 knockdown. In conclusion, our findings highlight that the lncRNACROCCP2/miR-5584-5p/HOXD11 axis promotes glioma progression by suppressing autophagy, providing a potential novel strategy for targeted therapy.