Table 2.

LncRNA CCAT2 role in cervical cancer progression

Cancer	Expression	Model	Target/pathway	Main findings	Refs.
CC	Upregulated	Serum of CC patients and healthy control	CCAT2/Wnt/β-catenin	-↑ Serum CCAT2 in CC vs. CIN healthy controls. -↑ CCAT2 expression = advanced tumor stages lymph node metastasis. - Prognostic factor	[1]
CC	Upregulated	CC patients tissue, BALB/c nude mice, HeLa/SiHa cells	miR-493-5p/CREB1/CCAT2	- ↑ CCAT2 in CC vs. NC - Knockdown CCAT2 → ↓ proliferation, migration, invasion - CCAT2 acts as a ceRNA → ↑ CREB1 by sponging miR-493-5p	[2]
CC	Downregulated	HeLa, CaSki, SiHa, CCK8 (Dojindo), BD Biosciences	1. CCAT2/MYC/miR-17-5p/miR-20a/TCF7L2/WNT 2. CCAT2/PI3K/Akt/Crk	CCAT2 is↑ expressed in HeLa and other CC cell lines - knockdown→↓ cell proliferation, G1 phase arrest,↑ Apoptosis	[5]
CC	Upregulated	CESC patients tissue, qRT-PCR, Kaplan-Meier survival analysis	lncRNA CCAT2/FIGO stage/lymph node metastasis/depth of cervical invasion	-CCAT2 is ↑ in CESC tissues -↑ expression →advanced FIGO stages, lymph node metastasis, and deeper cervical invasion -Poor prognostic factor for OS and PFS in CSCC patients.	[3]
CC	Upregulated	CESC patients tissue, Healthy females tissue	MYC/Wnt/CCAT2	- rs6983267 SNP → Advanced stage III SCC higher grades (G2, G3). - rs6983267 G allele → ↑ MYC transcript levels in CSCC non-cancerous cervical tissues. -rs6983267 SNP → ↑ risk of CSCC in individuals with: Oral contraceptive use, Tobacco smoking, Postmenopausal age	[4]
CC	Upregulated	Serum samples from CESC patients, CIN patients, healthy controls	Wnt/MYC/lncRNA CCAT2	lncRNAs (CCAT2, LINC01133, and LINC00511) ↑ in CESC patients’ -high diagnostic potential with an AUC of 0.94 in ROC analysis.	[6]

lncRNA: long non-coding RNA, CC: Cervical Cancer, NC: Normal Cells, CIN: Cervical Intraepithelial neoplasia, EMT: Epithelial Mesenchymal Transition, ceRNA: competing endogenous RNA, siRNA: Small Interfering RNA, CESC: Cervical Squamous Carcinoma, ROC: Receiver Operating Characteristics, AUC: Area Under Curve, CCAT2: Colon Cancer Associated Transcript 2, miR-493-5p: MicroRNA 493- 5 prime strand, CREB1: cAMP response element-binding protein 1, CCK8: Cell Counting Kit-8, BD Biosciences: Becton, Dickinson and Company Biosciences, miR-17-5p: MicroRNA 17 − 5 prime strand, miR-20a: MicroRNA 20a, TCF4:TCF7L2: T-cell factor 7-like 2, PI3K: Phosphoinositide 3-kinase, Akt: Protein kinase B, Crk: CT10 regulator of kinase, WNT: Wingless-related integration site, OS: overall survival, PFS: progression-free survival, CSCC: cervical squamous cell cancer, MYC: myelocytomatosis oncogene, SNP: Single Nucleotide Polymorphism, SCC: Squamous Cell Carcinoma