Table 3.

Noncoding RNAs regulates ferroptosis in cancer metastasis.

Noncoding RNAs	Target gene	Function in human cancer metastasis
LncRNA
MIR503HG	miR-1273c [99] EMT-related proteins [173]	The expression of lncRNA MIR503HG was decreased in bladder cancer tissues, which was associated to lymph node metastasis. Overexpression of MIR503HG inhibited tumor metastasis by decreasing the EMT-related protein levels, such as ZEB1, Snail, N-cadherin, etc. [173]. In hepatocellular carcinoma, lncRNA miR503HG exerted a metastatic tumor suppression role by inhibiting NF-kB pathway via modulating HNRNPA2B1 ubiquitination [174]. Importantly, treatment with XAV939 decreased the expression of lncRNA MIR503HG by sponging miR-1273c and regulating SOX4 level. The XAV939 induced decreased expression of SLC7A11 suppressed NSCLC development through the ferroptosis pathway [99].
MT1DP	MDA and ROS [100] ADAM10-JAK-STAT [101]	Overexpression of lncRNA MT1DP promoted MDA production and ROS levels, which sensitized lung cancer cells to erastin-induced ferroptosis [100]. It has reported miR-365a-3p inhibited metastasis of colorectal cancer by regulating ADAM10-JAK-STAT pathway [101].
PVT1	miR-214 [102] miR-361-3p/SOX9 [175] miR-145 [176] miR-526b/FOXC2 [177] miR-484 [178] miR-106a-5p/HK2 [179] miR-125 [180] miR-186-5p [181]	Lnc RNA PVT1 promoted ferroptosis in vivo by down-regulating miR-214 and exsisted a positive feedback loop of lncRNA PVT1/miR-214/p53 [102]. PVT1 was reported to promoted metastasis of various human cancers such as lung cancer [175, 182], CRC [176], osteosarcoma [178], hepatocellular carcinoma [181], gastric cancer cells [180] and oral squamous cell carcinoma [179].
ZFAS1	miR-150-5p/SLC38A1 [103]	Interference with ZFAS1 inhibited ferroptosis by sponging miR-150-5p to down-regulate the expression of SLC38A1 [103]. Meanwhile, MiR150 was closely related to the metastasis of nasopharyngeal carcinoma [183].
Circ RNAs
Circ_0008035	miR-599/EIF4A1 [104] miR599/c-Myc [184]	Circ_0008035 was increased in GC tissues to suppress ferroptosis via miR-599/EIF4A1 axis [104]. Additionally, miR599/c-Myc pathway was also involved in the metastasis of esophageal squamous cell carcinoma [184].
CircABCB10	miR-326/CCL5 [105] miR-326/SLC27A4 [185] miR-326/FSCN1 [186] miR-326/TWIST1[187]	Interference with circABCB10 suppressed the cell ferroptosis by regulating the miR-326/CCL5 axis in rectal cancer. CircABCB10 and CCL5 were upregulated but miR-326 was downregulated in rectal cancer [105]. Moreover, miR-326 promoted metastasis in gastric cancer [186], lung cancer [188], liver cancer [185], and endometrial cancer [187].
CircIL4R	miR-541-3p/GPX4 [106] miR-541-3p/TMPRSS4 [189]	circIL4R was abnormally overexpressed in HCC. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells by the miR-541-3p/GPX4 network [106]. It has also reported miR-541-3p inhibited the migration of HCC cells via suppressing the level of TMPRSS4 [189].
Circ-TTBK2	miR-761/ ITGB8 [107] miR-761/ING4 and TIMP2 [190] miR-761/Ras [191]	circ-TTBK2 knockdown suppressed invasion, and promoted ferroptosis via targeting ITGB8 by sponging miR-761 in glioma[107]. MiR-761 promoted metastasis of NSCLC by targeting ING4 and TIMP2 [190].
miRNAs
miR-202	PIK3CA [192]	lncRNA MALAT1 promoted osteosarcomas metastasis by sponging miR202 [193]. miR202 inhibited prostate cancer metastasis by targeting PIK3CA [192]
miR-103a-3p	GLS2 [194] KLF4 [195] LATS2 [196] DAPK and KLF4 [197]	miR-103a promoted metastasis of gastric cancer by targeting KLF4 [195], and promoted metastasis of hepatocellular carcinoma by inhibiting LATS2 [196]. Moreover, PG exerted anti-tumor role in gastric cancer (GC) by downregulating inhibitory effect of miR-103a-3p on glutaminase 2 (GLS2) expression, which was involved in ferroptosis during the progression of GC [194].
miR-214-3p	ATF4 [111]	MicroRNA-214-3p promoted ferroptosis in hepatoma cells partly by decreased the expression of ATF4, which obviously decreased the size and weight of xenografted tumors [111]
miR-137	SLC1A5 [112]	miR-137 negatively regulated ferroptosis by regulating SLC1A5 in melanoma. However, interference with miR-137 increased the antitumor effects of erastin by promoting ferroptosis, suggesting promotion of ferroptosis was a potential treatment for melanoma [112].
miR-17-92	A20-ACSL4 [113]	miRNA-17-92 is an oncogenic miRNA which is associated with lymph node metastasis in oesophageal adenocarcinoma [198]. But in gastric cancers, miRNA-17-92 was negatively associated with metastasis [199]. Overexpression of miR-17-92 suppressed the cell death of endothelial HUVEC cells and reduced ROS generation. Moreover, miR-17-92 suppressed the erastin-induced ferroptosis [113].
miR-4715-3p	AURKA [115] RAC1 [200]	The miR-4715-3p were methylated in upper gastrointestinal adenocarcinoma (UGC). Knockdown of miR-4715-3p in UGCs inhibited GPX4 induced cell death [115]. Interference with LCAT1 inhibited metastasis in the mouse xenografts mediated by miR-4715 [200].
miR-522	ALOX15 [116] DENND2D [201]	lipoxygenase 15 (ALOX15) was associated to lipid-ROS production in human gastric cancer, and exosome-miR-522 worked as a potential inhibitor of ALOX15 [116]. Interference with miR-522 inhibited metastasis of NSCLCs by directly targeting DENN/MADD domain containing 2D (DENND2D) [201].
miR-212-5p	Ptgs2 [117] Sirt2 [202] TCF7L2 [203]	miR-212-5p attenuated ferroptotic neuronal death by targeting Ptgs2 [117]. Additionally, miR-212-5p regulated cancer metastasis by targeting Sirt2 in colorectal cancer [202] and TCF7L2 [203] in human cervical cancer.
miR-23a-3p	DMT1 [118] CDH1 [204] TSGA10 [205] Sprouty2 [206]	HUCB-MSCs-exosomes inhibited DMT1, the target gene of miR-23a-3p to suppress ferroptosis and decrease myocardial injury [118]. miR-23a regulated metastasis of various human cancers with different mechanism. For instance, interference with miR-23a facilitated metastasis of cutaneous melanoma [207], but it also promoted mammary carcinoma cell metastasis by targeting Sprouty2 [206].
miR-30d	FTH1 and GPX4 [119] SOX9 [208]	Interference with miR-30d increased the expression of FTH1 and GPX4 in H9C2 cells to promote ferroptosis [119]. miR-30d was reported to involved in regulation the metastasis of retinoblastoma cells via miR-30d/SOX9/ZEB2 [208].