Recent advances on regulatory roles of HuD and promoter hypermethylation for miR-204 in lung cancer development

Table 1 Dysregulation of miR-204 and downstream oncogenic axes in small cell lung cancer and non-small cell lung cancer subtypes

Comparison item	Mechanism	Upstream driving factors	The influence on miR-204	Main downstream effector molecules	Clinical significance	Ref.
SCLC	HuD-regulated axis	HuD binds and stabilizes LYPLAL1-DT and PFN2 mRNA	Indirectly inhibit miR-204-5p	PFN2	Elevated levels of HuD, LYPLAL1-DT, and PFN2 correlate with reduced PFS/OS	[19,29]
NSCLC (LUAD/LUSC)	DNMT-mediate promoter hypermethylation	Promoter hypermethylation	Directly inhibit miR-204-5p	NUAK1 → Activate the mTOR pathway	Increased NUAK1 expression and poor prognosis	[21,40]
	LINC00483 axis (LUAD)	Significantly upregulate LINC00483	Sponging, miR-204-3p	ETS1	High LINC00483 expression correlates with shorter LUAD survival, advanced TNM stage, larger tumors, and positive lymph node metastasis	[44,45]
	LINC01980 axis (LUSC)	High expression of LINC01980	Directly inhibit miR-204-3p	The specific target gene has not been clearly identified	Elevated LINC01980 expression associated with increased malignancy in LUSC	[46]

SCLC: Small cell lung cancer; NSCLC: Non-small cell lung cancer; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma.