Table 2.

The role of RCAN1 in various tumors

Cancer types	Tumor tissue expression: down-or upregulated	Function: Inhibition or promotion	How to regulate RCAN1	The specific signaling pathways downstream of RCAN1	Clinical significance	References
Breast cancer	Downregulated	Inhibition	RUNX3 resulted in a decreased RCAN 1.4 expression; oxytocin induced nuclear translocation of NFAT to induce expression of RCAN1	RCAN1.4 Inhibited CN-NFAT2 signaling	–	Deng et al. (2020); Behtaji et al. (2021)
Lung cancer	Downregulated	Inhibition	Hypoxia induced the release of specific exosome miR-619-5p and inhibited RCAN1.4	Modulated the level of VEGF-VEGFA; blocking of CN—NFAT signaling and CN-NFAT—angiopoietin-2 signaling axis	Arsenic trioxide (As2O3) inhibited SCLC metastasis by upregulating RCAN1	Baek et al. (2009); Kim et al. (2020); Shin et al. (2014); Minami et al. (2013); Ma et al. (2017); Zheng et al. (2019)
Hepatocellular carcinoma	Downregulated	Inhibition	miRNAs (miR-877, miR‐572 and miR-182-5p) negatively regulated RCAN1; aberrant CpG methylation in the 5’ regulatory region of RCAN1.4 induced RCAN1.4 down-regulation	RCAN1.4 inhibited IGF-1 and VEGFA by inhibiting CN—NFAT1 signaling	–	Jin et al. (2017); Song et al. (2019); Shi et al. (2018)
Pancreatic carcinoma	Downregulated	Inhibition	–	RCAN1.4 inhibited IFI27 and VEGFA by inhibiting CN—NFAT1 signaling	–	Lao et al. (2021); Lee et al. (2013)
Colorectal carcinoma	Downregulated	Inhibition (Targeted RCAN1 deletion suppresses tumor growth)	PPARγ positively regulated RCAN1	Inhibited CN-NFAT signaling pathway	As a biomarker to predict recurrence in stages II and III of colon cancer	Ryeom et al. (2008); Espinosa et al. (2009); Sebio et al. (2015); Bush et al. (2007)
Renal carcinoma	Downregulated	Inhibition (Targeted RCAN1 deletion suppresses tumor growth)	–	Regulated VEGF-CN-NFAT signaling	RCAN1.4 reduced sunitinib resistance	Ryeom et al. (2008); Song et al. (2018)
Bladder cancer	Downregulated	–	–	–	The level of RCAN1 expression in urine enabled diagnosis of bladder cancer	Eissa et al. (2019)
Endometrial adenocarcinoma	Downregulated	Inhibition	–	Inhibited CN-NFAT signaling pathway to negatively regulate the expression of CXCL8, IL-8, and IL-11	–	Sales et al. (2009); Maldonado-Pérez et al. (2009); Sales et al. (2010)
Epithelial ovarian cancer	–	Not significantly affected	–	–	–	Hata et al. (2009)
Thyroid cancer	Downregulated	Inhibition	Metastin enhanced the expression of RCAN1	Inhibited NFE2L3 and CN-NFAT signaling	–	Wang et al. (2017); Espinosa et al. (2009); Stathatos et al. (2005))
Oral squamous cell carcinoma	Downregulated	Inhibition	miR-103a-3p downregulated RCAN1	–	–	Zhang et al. (2020)
Hypopharyngeal and Laryngopharynx cancer	Upregulated	Promotion	–	Activated VEGF signaling pathway	–	Lv et al. (2017); Lü et al. (2011)
Leukaemia and other hematonosis	–	Inhibition	GC/CR complex induced RCAN1.1	RCAN1.1 inhibited CN activity	RCAN1.1 increased sensitivity to GC and enhanced sensitivity to LEN in MDS/AML	Saenz et al. (2015); Hirakawa et al. (2009); Nagao et al. (2012); Shen et al. 2004)
Lymphoma and Glioma	–	Inhibition	–	Inhibited NF-κB		Liu et al. (2015b); Chen et al. (2017)