Cell Cycle-Related lncRNAs as Innovative Targets to Advance Cancer Management

Figures & data

Figure 1 LncRNAs associated with various types of cancer.

Table 1 The Regulation of lncRNAs on Cyclin in Tumors

LncRNA	Cancer types	Expression	Functions	Related gene	Reference
HOTAIR	GC	Upregulated	Promoted the proliferation of cancer cells	miR-454-3p, CCND1, STAT3	[16]
TTTY15	GC	Upregulated	Promoted cancer progression	miR-98-5p, CCND2	[17]
PVT1	GC	Upregulated	Promoted cancer cell proliferation, invasion, and cell cycle progression	miR-16, CCND1	[18]
LINC01667	GC	Upregulated	Promoted the proliferation of cancer cells	miR-138-5p, CCNE1	[19]
LINC00152	HCC	Upregulated	Promoted cancer cell proliferation	miR-193a-3p, CCND1	[20]
PR11-295G20.2	HCC	Upregulated	Promoted cancer cell proliferation, invasion, and migration	miR-6884-3p, CCNB1	[21]
LINC01488	HCC	Downregulated	Inhibited metastasis and tumorigenesis	miR-124-3p, miR-138-5p, CCNE	[22]
CASC9	Pancreatic Cancer	Upregulated	Promoted cancer progression	miR-497-5p, CCND1	[23]
XIST	ESCC	Upregulated	Promoted cell cycle progression, proliferation, migration, invasion, and inhibited cell apoptosis	miR-129-5p, CCND1	[24]
LINC01234	EC	Upregulated	Promoted cancer cell proliferation and inhibited apoptosis	miR-193a-5p, CCNE1	[25]
HOXD-AS1	CRC	Upregulated	Promoted the proliferation, invasion and migration of cancer cells	miR-526b-3p, CCND1	[26]
MCF2L-AS1	CRC	Upregulated	Promoted the proliferation of cancer cells	miR-874-3p, CCNE1	[27]
HNF1A-AS1	CRC	Upregulated	Promoted the proliferation, migration and angiogenesis, accelerated cell cycle and reduced apoptosis	miR-93-5p, PDCD4, CCND1	[28]
CDKN2B-AS1	RCC	Upregulated	Promoted cancer cell invasion	miR-141, CCND1, CCND2	[29]
LOXL1-AS1	PC	Upregulated	Regulated cancer cell proliferation and cell cycle progression	miR-541-3p, CCND1	[30]
ADAMTS9-AS1	PC	Downregulated	Inhibited cancer progression	miR-142-5p, CCND1	[31]
MALAT1	Bladder cancer	Upregulated	Promoted cancer cell proliferation and migration	miR-34a, CCND1	[32]
LINC01355	BC	Downregulated	Inhibited cancer progression	CCND1	[33]
GACAT3	BC	Upregulated	Promoted cancer progression	miR-497, CCND2	[34]
LINC00473	BC	Upregulated	Promoted cancer progression	miR-424-5p, CCNE1	[35]
HOTAIR	OC	Upregulated	Promoted cancer cell proliferation, cell cycle progression, migration and invasion	miR-206, CCND1, CCND2	[36]
PCAT-1	EOC	Upregulated	Regulated the proliferation, migration and invasion of cancer cells	CCND1, CDK4	[37]
CRNDE	CC	Upregulated	Regulated the proliferation, migration and invasion of cancer cells.	miR-183, CCNB1	[38]
Lnc_000231	CC	Upregulated	Promoted cancer cell proliferation and tumor formation	miR-497-5p, CCNE1	[39]
TINCR	CSCC	Upregulated	Promoted cancer cell proliferation	miR-302, CCND1	[40]
PCNA-AS1	NSCLC	Upregulated	Promoted cancer cell proliferation	CCND1	[41]
Linc00703	NSCLC	Downregulated	Inhibited cancer cell proliferation	CCND1, CDK4	[42]
MCF2L-AS1	NSCLC	Upregulated	Promoted cancer progression	ELAVL1, CCND1	[43]
Linc00467	LUAD	Upregulated	Promoted cancer cell proliferation	miR-20b-5p, CCND1	[44]
PTPRG-AS1	LUAD	Upregulated	Promoted cancer cell proliferation and cell cycle progression	miR-124-3p, CCND1	[45]
RP11-805J14.5	LUAD	Downregulated	Inhibited cancer progression	miR-139-5p, miR-34b-3p, CCND2	[46]
FLVCR-AS1	OS	Upregulated	Promoted cancer cell proliferation	miR-381-3p, CCND1	[47]
NR2F1-AS1	TC	Upregulated	Promoted the proliferation and migration of cancer cells	miR-338-3p, CCND1	[48]
LINC00887	Glioma	Upregulated	Promoted malignant progression of cancer	CCND1	[49]
RUNX1-IT1	GBM	Upregulated	Promoted cancer cell proliferation	miR-195, CCND1	[50]
HCP5	MM	Upregulated	Promoted cancer progression	miR-128-3p, PLAGL2, CCND1	[51]
PVT1	Pituitary adenoma	Upregulated	Promoted the proliferation and migration of cancer cells	CCND1	[52]

Abbreviations: GC, Gastric Cancer; HCC, Hepatocellular Carcinoma; ESCC, Esophageal Squamous Cell Carcinoma; EC, Esophageal Carcinoma; CRC, Colorectal Cancer; RCC, Renal Cell Carcinoma; PC, Prostate Cancer; BC, Breast Cancer; OC, Ovarian cancer; EOC, Epithelial ovarian cancer; CC, Cervical cancer; CSCC, Cervical Squamous Cell Carcinoma; NSCLC, Non-Small Cell Lung Cancer; LUAD, Lung Adenocarcinoma; OS, Osteosarcoma; TC, Thyroid Cancer; GBM, Glioblastoma; MM, Multiple Myeloma.

Table 2 The Regulation of lncRNAs on CDK in Tumors

LncRNA	Cancer Types	Expression	Functions	Related Gene	Reference
GCRL1	GC	Upregulated	Promoted cancer cell proliferation and migration	CDK4, miR-885-3p	[55]
LINC00974	GC	Upregulated	Promoted the proliferation of cancer cells	CDK6	[56]
LINC00630	HCC	Upregulated	Promoted the malignant progression of cancer	CDK2, E2F1	[57]
VPS9D1-AS1	HCC	Upregulated	Regulated the proliferation of cancer cells	CDK4, HuR protein	[58]
LINC00205	HCC	Upregulated	Promoted the proliferation of cancer cells	CDK6, YY1, miR-26a-5p	[59]
CRNDE	HCC	Upregulated	Promoted proliferation, invasion and migration	CDK6, miR-33a-5p	[60]
MCM3AP-AS1	CRC	Upregulated	Promoted cell cycle progression	CDK4, miR-545	[61]
NR2F2-AS1	Colon Cancer	Upregulated	Promoted the proliferation of cancer cells	CDK6	[62]
CASC21	CRC	Upregulated	Promoted the proliferation of cancer cells	CDK6, miR-539-5p	[63]
HAGLR	CRC	Upregulated	Promoted cancer progression	CDK4/6, miR-185-5p	[64]
UCA1	ACC	Upregulated	Promoted cancer cell growth	CDK6, miR-298	[65]
HOST2	TNBC	Upregulated	Promoted the proliferation of cancer cells	CDK6, let-7b	[66]
SNHG15	OC	Upregulated	Promoted the proliferation of cancer cells	CDK6, miR-370-3p	[67]
LINC00313	CC	Upregulated	Promoted cancer cell proliferation and migration	CDK6, miR-4677-3p	[68]
MACC1-AS1	CSCC	Upregulated	Promoted proliferation and cell cycle	CDK6, miR-34a	[69]
NR2F2-AS1	PC	Upregulated	Promoted the proliferation of cancer cells	CDK4	[70]
LINC01194	NSCLC	Upregulated	Promoted the proliferation of cancer cells	CDK4, miR-486-5p	[71]
FOXD3-AS1	NSCLC	Upregulated	Promoted proliferation, inhibited apoptosis	CDK6, miR-135a-5p	[72]
HNF1A-AS1	NSCLC	Upregulated	Promoted proliferation, invasion and migration	CDK6, miR-149-5p	[73,74]
MEG8	NSCLC	Upregulated	Promoted proliferation, invasion and migration	CDK6, miR-107	[75]
AWPPH	NSCLC	Upregulated	Promoted malignant progression of cancer	CDK6, miRNA-204	[76]
TFAP2A-AS1	NSCLC	Upregulated	Promoted cancer progression	miR-584-3p, CDK4	[77]
91H	OS	Upregulated	Promoted cancer progression	CDK4	[78]
LOC100129620	OS	Upregulated	Promoted proliferation, invasion and migration	CDK6, miR-335-3p	[79]
SNHG6	PTC	Upregulated	Promoted the proliferation of cancer cells	CDK6, miR-186	[80]
PCGEM1	Glioma	Upregulated	Promoted cancer progression	CDK6, miR-539-5p	[81]
H19	Glioma	Upregulated	Promoted growth, invasion and migration	CDK6, miR-200a, ZEB1	[82]
HAND2-AS1	Glioma	Upregulated	Regulated the proliferation, invasion and migration of cancer cells	CDK6	[83]
LINC00704	NPC	Upregulated	Promoted growth and cell cycle	CDK6, ETS1	[84]

Abbreviations: GC, Gastric Cancer; HCC, Hepatocellular Carcinoma; CRC, Colorectal Cancer; ACC, Adrenocortical Carcinoma; TNBC, Triple Negative Breast Cancer; OC, Ovarian cancer; CC, Cervical cancer; CSCC, Cervical Squamous Cell Carcinoma; PC, Prostate Cancer; NSCLC, Non-Small Cell Lung Cancer; OS, Osteosarcoma; PTC, Papillary Thyroid Cancer; NPC, Nasopharyngeal Carcinoma.

Figure 2 CDK-targeted cell cycle regulation in NSCLC mediated by lncRNA. LINC01194 regulated the miR-486-5p/CDK4 axis and FOXD3-AS1 interacted with miR-135a-5p/CDK6 to promote the proliferation of NSCLC cells. HNF1A-AS1 regulated the miR-149-5p/CDK6 axis and MEG8 interacted with miR-107/CDK6 to facilitate proliferation, invasion and migration of NSCLC. AWPPH/miRNA-204/CDK6 regulatory loop was identified to aggravate the malignant progression of NSCLC and TFAP2A-AS1 contributed to cancer progression by regulating the miR-584-3p/CDK4 axis.^71–77

Figure 3 Mechanism of lncRNA ANRIL-mediated regulation of the INK4 locus. LncRNA ANRIL binds to the INK4 locus and interacts specifically with SUZ12 in the PRC2 complex and with CBX7 in the PRC1 complex. ANRIL suppresses the INK4 locus by recognizing H3K27me3 and CBX7, and inhibits p15 transcription with SUZ12. E2F1 transcriptionally activates ANRIL in an ATM-dependent manner and participates in DNA repair. After DNA repair, ANRIL promoted cell growth and re-enters the cell cycle by repressing the INK4 locus.^88,89

Figure 4 The regulatory mechanism of lncRNAs involved in cancer cell cycle. The regulatory roles of lncRNAs on cancer cell cycle involve different mechanisms, including sponging by the ceRNA network, epigenetic modifications, transcription regulations and other regulatory pathways.

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