Long Noncoding RNA Mediated Regulation in Human Embryogenesis, Pluripotency, and Reproduction

Table 1

lncRNAs and their functions in reproductive diseases.

Diseases	lncRNA	Full name	Expression level	Assessed cell line	Signaling pathways and molecules	Functions	In other diseases	References
Nonobstructive azoospermia (NOA)	NLC1-C	Narcolepsy candidate-region 1 gene	Downregulated	NCCIT, NTERA-2 (NT2), HEK293 T	Sponge for miR-320a, miR-383	Inhibits miR-320a and miR-383 transcripts by binding to nucleolin, resulting in a hyperactive proliferation of germ cells	Testicular embryonal carcinoma	[71]
	GM2044	—	Upregulated	NCCIT	miR-202-Rbfox2 pathway	Inhibits the proliferation of the human testicular embryonic carcinoma cell NCCIT	—	[79]
	HOTAIR	Hox transcript antisense intergenic RNA	Downregulated	—	NRF2	Relates to defects in sperm function	Breast cancer, lung cancer, and pancreatic cancer	[80, 81, 123]
	Gadd7	lncRNA growth-arrested DNA damage-inducible gene 7	Upregulated	GC-1, GC-2	Bax, Bcl2	Inhibits cell growth and promotes apoptosis by upregulating the proapoptotic regulator Bax and downregulating the antiapoptotic regulator Bcl2	—	[82]
Prostate tumors	PRNCR1/PCGEM1	Prostate cancer-associated noncoding RNA 1/PCGEM1 prostate-specific transcript	Upregulated	LNCaP, LNCaP-cds1, LNCaP-cds2, CWR22Rv1	AR	Promotes the proliferation of prostate cancer cells	Breast cancer and lung cancer	[84, 124]
	NEAT1	Nuclear-rich transcriptase 1	Upregulated	LNCaP and PC3, RWPE1, VCaP and DU145	Estrogen receptor alpha (ERα)	Promotes the development of prostate cancer	Non-small-cell lung cancer, breast cancer, and hepatocellular carcinoma	[85, 125]
	PCAT-1	Prostate cancer-associated transcript-1	Upregulated	LNCaP	PRC2, cMyc	Promotes the proliferation of prostate cancer cells	Colorectal cancer, hepatocellular cancer, and gastric cancer	[86, 126]
	MALAT-1	Metastasis-associated lung adenocarcinoma transcript 1	Upregulated	LNCaP-AI, 22RV1	ZEB1, ZEB2, Slug	Is associated with the increase in the Gleason score, prostate-specific antigen (PSA), and tumor stage and promotes the invasion and growth of prostate cancer cells	Glioma, hepatocellular carcinoma, and multiple myeloma	[87, 127]
	SChLAP1	Second chromosome locus associated with prostate-1	Upregulated	—	—	Relates to poor prognosis and could be used as an important biomarker to identify patients with a high risk of lethal prostate cancer	Triple negative breast cancer and bladder cancer	[88, 128, 129]
	GAS5	Growth arrest specific 5	Downregulated	PC3, DU145, and PNT2C2	E2F1, P27^Kip1	Induces a cell cycle arrest in the G0–G1 phase and acts as a tumor suppressor	Colorectal cancer, gastric cancer, and melanoma	[89] [89, 130]
Ovarian cancer	XIST	Inactive X chromosome-specific transcripts	Downregulated	ALST, CAOV3, OVCA3, OVCA420, OVCA429, OVCA432, OVCA433, OVCA633, OVCA680, OVCA702, OVCA810, SKOV3, ES-2, TOV21G	XIAP	Downregulation of Xist may increase the expression of linked inhibitors of apoptosis protein and lead to the phenotype of drug	Non-small-cell lung cancer, breast cancer, and primary hepatocellular carcinoma	[91, 131, 132]
	H19	Imprinted maternally expressed transcript	Upregulated	SKOV3, OV90, TOV112D, ES2	Caspase-3, caspase-9, Bax, Bcl-2, cyclin B1/Cdc2	Promotes ovarian cancer cell proliferation	Head and neck cancer, pancreatic cancer, and osteosarcoma	[92, 93, 133]
	MALAT1	Metastasis-associated lung adenocarcinoma transcript 1	Upregulated	SKOV3, SKOV3.ip1, 293T	—	Promotes cell proliferation and metastasis and inhibits cell apoptosis	Glioma, hepatocellular carcinoma, and multiple myeloma	[94–96, 127]
	LINC00565	Long intergenic nonprotein coding RNA 565	Upregulated	OVCAR3, SKOV3, HO8910, A2780, and HEY	GAS6, cyclinE1, cyclinD1, CDK4 P16, P21	Relates to the FIGO (International Federation of Gynecology and Obstetrics) stage, cell cycle, and size of tumor cells and promotes cell proliferation, invasion, and migration	Gastric cancer and colorectal cancer	[97, 134, 135]
	DARS-AS1	DARS1 antisense RNA 1	Upregulated	A2780, SKOV3, and OVCAR-3	Sponge for miR-532-3p	Promotes the proliferation, migration, and invasion of ovarian cancer cells	Thyroid cancer, clear cell renal cell carcinoma, and non-small-cell lung cancer	[98, 136, 137]
	FEZF1-AS1	FEZF1 antisense RNA 1	Upregulated	SKOV-3, HO8910, HO8910PM, ES2, and HG-SOC	JAK-STAT3 pathway	Relates to poor prognosis, promotes cell proliferation, and inhibits cell apoptosis	Colorectal cancer, gastric neoplasia, and hepatocellular carcinoma	[99, 138]
	LEF1-AS1	LEF1 antisense RNA 1	Upregulated	SKOV3, OVCAR3	miR-1285-3p	The absence of LEF1-AS1 results in inhibiting proliferation, migration, and invasion of ovarian cancer cells	Glioblastoma, colorectal cancer, and retinoblastoma	[100, 139–141]
Endometrial carcinoma (EC)	H19	Imprinted maternally expressed transcript	Upregulated	—	—	Regulates migration and invasion of the tumor cells	Head and neck cancer, pancreatic cancer, and osteosarcoma	[102, 133]
	CCAT1	Colon cancer-associated transcript 1	Upregulated	HEC-1-A, KLE, Ishikawa	Sponge for miR-181a-5p	Promotes the proliferation and migration of endometrial cancer cells	Breast cancer and multiple myeloma	[103, 142]
	MIR22HG	MIR22 host gene	Downregulated	HEC-1 A, KLE	Sponge for miR-141-3p	Inhibits the proliferation and migration and promotes the apoptosis of cancer cells	Esophageal cancer, lung cancer, and hepatocellular carcinoma	[104, 143]
	MEG3	Maternal expression gene 3	Downregulated	Ishikawa, HEC-1B	PI3K/m-TOR pathway, BclxL, VEGFA	High expression of MEG3 inhibits the migration, invasion, and proliferation of EC cells and increases apoptosis	Gastric cancer, osteosarcoma, and breast cancer	[105, 144]
Endometriosis	AC002454.1	—	Upregulated	—	CDK6	Promotes the migration, invasion, and proliferation of cells and regulates the cell cycle	Bladder cancer	[107, 145]
	MALAT1	Metastasis-associated lung adenocarcinoma transcript 1	Upregulated	—	NF-κB/iNOS pathway, MMP-9, caspase-3	Promotes the proliferation and migration of endometrial cells	Glioma, hepatocellular carcinoma, and multiple myeloma	[108, 127]
	AFAP1-AS1	Actin filament-associated protein 1; Antisense RNA1	Upregulated	Ishikawa	ZEB1	Promotes the EMT process of endometriosis	Esophageal cancer, pancreatic ductal adenocarcinoma	[109, 146]
	CCDC144NL-AS1	CCDC144NL antisense RNA 1	Upregulated	hEM15A	MMP-9, F-actin, vimentin	Affects the cytoskeleton structure and promotes cell invasion and migration	Osteosarcoma, gastric cancer, non-small-cell lung cancer, and hepatocellular carcinoma	[110, 147–150]
	TC0101441	—	Upregulated	ECSCs	TCF8/ZEB1, slug, snail, and N-cadherin	EV shuttling of TC0101441 promotes invasion and migration of endometriosis	Gastric cancer	[151, 152]
	UCA1	Urothelial carcinoma-associated-1	Downregulated	—	—	Is involved in the pathogenesis of endometriosis and can be used as a biomarker for diagnosis and prognosis	Urothelial carcinoma-associated 1 gastric cancer and colorectal cancer	[153, 154]
	H19	Imprinted maternally expressed transcript	Downregulated	293T, HESCs	H19/Let-7/IGF1R, H19/miR-216a-5p/ACTA2 pathway	Regulates endometrial stromal cell proliferation, invasion, and migration	Head and neck cancer, pancreatic cancer, and osteosarcoma	[133, 155, 156]
	aHIF	Antisense hypoxia-inducible factor	Upregulated	ECSCs, HUVECs	(VEGF)-A, VEGF-D	Facilitates endometriosis angiogenesis and is used as a potential biomarker and therapeutic target for endometriosis	Gastric cancer, glioblastoma multiforme, and paraganglioma	[157–159]
Cervical cancer	MALAT1	Metastasis-associated lung adenocarcinoma transcript 1	Upregulated	—	HeLa, CaSki	Promotes the proliferation and invasion of cervical cancer cells and reduces apoptosis	Glioma, hepatocellular carcinoma, and multiple myeloma	[112, 127]
	HOTAIR	Hox transcript antisense intergenic RNA	Upregulated	SiHa, HeLa, Caski	VEGF, MMP-9, E-cadherin, β-catenin, vimentin, snail, twist	Promotes metastasis and invasion of tumor cells	Breast cancer, lung cancer, and pancreatic cancer	[113, 123]
	RP11-480I12.5	—	Upregulated	PCS-480-011, SiHa (HTB-35), HeLa229 (CCL-2.1), and MS751	Wnt/β-catenin pathway	Induces EMT through the Wnt/β-catenin pathway and promotes migration, invasion, and proliferation of cervical cancer cell lines	Breast cancer	[114, 160, 161]
	RP1-93H18.6	—	Upregulated	SiHa, HeLa, CaSki, and C-33A	PI3K/Akt/mTOR pathway	Promotes growth and metastasis of tumor cells and reduces apoptosis	—	[115]
	DSCAM-AS1	DSCAM antisense RNA 1	Upregulated	SiHa, HeLa, C-33A, and CaSki	Sponge for miR-361-5p	Enhances the ability of cells to migrate, invade, and proliferate and promotes the development of cervical cancer	Non-small-cell lung cancer, colorectal cancer, and osteosarcoma	[116, 162]
	GAS5-AS1	GAS5 antisense RNA 1	Downregulated	Caski, SiHa, C33A, and HeLa	GAS5	Relates to the FLGO stage, lymphatic metastasis, distant metastasis, and poor prognosis and promotes proliferation, migration, and invasion	Glioma, non-small-cell lung cancer, and hepatocellular carcinoma	[117, 153, 163, 164]
	PVT1	Plasmacytoma variant translocation-1	Upregulated	HeLa and SiHa	Sponge for miR-140-5p, Smad3	Promotes the proliferation and metastasis of cervical cancer	Clear cell renal cell carcinoma and thyroid cancer	[118, 165]
Polycystic ovary syndrome (PCOS)	H19	Imprinted maternally expressed transcript	Upregulated	Peripheral blood leukocytes	FPG	May be a key factor in endocrine and metabolic diseases in patients with PCOS	Head and neck cancer, pancreatic cancer, and osteosarcoma	[120, 133]
	PVT1	Plasmacytoma variant translocation-1	Upregulated	—	Sponge for miR-17-5p	Regulates the apoptosis and the proliferation of ovarian granulosa cells	Clear cell renal cell carcinoma and thyroid cancer	[165, 166]
	LET	Low expression in tumor	Downregulated	KGN	Wnt/β-catenin and Notch pathways, TIMP2	Promotes cell migration and survival and inhibits cell apoptosis	Hepatocellular carcinoma, colorectal cancer, and squamous cell lung carcinoma tissues	[167, 168]
	TMPO-AS1	TMPO antisense RNA 1	Upregulated	COV434	Sponge for miR-355-5p	Serve as a potential target to treat PCOS	Lung cancer, breast cancer, and colorectal cancer	[169, 170]
	NEAT1	Nuclear-rich transcriptase 1	Upregulated	Ovarian tissue in rats	Sponge for miR-381, IGF1	Promotes cell proliferation and represses cell apoptosis	Non-small-cell lung cancer, breast cancer, and hepatocellular carcinoma	[125, 171]
	LINC00477	Long intergenic nonprotein coding RNA 477	Upregulated	Sponge for miR-128	Sponge for miR-128	LINC00477/miR-128 axis may represent a potential method for the treatment of PCOS	Gastric cancer	[172, 173]