Knockdown of long non‑coding RNA CCAT2 suppresses the progression of thyroid cancer by inhibiting the Wnt/β‑catenin pathway

Abstract

Thyroid cancer (TC) is one of the most common malignancies with a high mortality rate. Long non-coding RNA CCAT2 (CCAT2) participates in the occurrence and development of certain human cancers; however, whether it is involved in TC remains unclear. Thus, the present study investigated the role of CCAT2 in TC and the underlying mechanism. CCAT2 expression in both TC tissues and cell lines was examined by reverse transcription-quantitative PCR. CCAT2 expression was silenced in TC cell lines by a specific small interfering (si)RNA against CCAT2 (si-CCAT2). The effects of CCAT2 silencing on TC cell proliferation were detected by CCK-8 and colony formation assays. Cell cycle and apoptosis of the treated TC cells were assessed by flow cytometry. Wound healing and Transwell assays were performed to detect the effects of si-CCAT2 on the migration and invasion of TC cells. Apoptosis-related proteins and Wnt/β-catenin cascade-associated agents were examined by western blotting. The interaction between CCAT2 and the Wnt/β-catenin pathway in the transfected cells was detected by performing a dual-luciferase reporter assay. CCAT2 expression was increased in TC tissue samples and cell lines compared with the controls. Tissue CCAT2 level was associated with T stage and tumor-node-metastasis stage of TC. Silencing CCAT2 inhibited TC cell proliferation, migration and invasion, and promoted TC cell cycle arrest and apoptosis. Furthermore, CCAT2 knockdown suppressed the activity of the Wnt/β-catenin cascade in TC cells treated with lithium chloride. In summary, the present study demonstrated that CCAT2 knockdown suppresses TC progression via inactivating the Wnt/β-catenin cascade, indicating that suppressing CCAT2 and the Wnt/β-catenin signaling pathway may be a promising therapeutic strategy for treating TC.

Long non-coding RNA colon cancer-associated transcript 2: role and function in human cancers

“…In 2020, Xin et al [ 3 ] revealed elevated expression levels of CCAT2 in TC cell lines and tissues. Moreover, the level of CCAT2 in tissues was related to the T stage of the tumor and tumor metastasis.…”

“…Inhibiting the CCAT2 expression may suppress the proliferative, migratory, and invasive abilities of tumor cells, thus enhancing cell apoptosis and cell cycle arrest in CRC, [ 6 ] lung cancer, [ 21 ] neuroblastoma, [ 1 ] breast cancer, [ 69 ] CCA, [ 53 ] ovarian cancer, [ 64 , 65 ] and other tumors. [ 3 , 6 , 12 , 28 , 34 , 62 , 76 , 78 ] Furthermore, in vivo studies have shown that inhibiting the expression of CCAT2 can inhibit the growth of breast cancer, [ 69 ] HCC, [ 50 ] lung cancer, [ 21 ] and other cancer cells. In addition, Sun et al [ 18 ] pointed out that knocking out the expression of CCAT2 in glioma cells can significantly inhibit the growth and endothelial angiogenesis and also induce early glioma cells’ apoptosis.…”

“…[7] In addition, the rs6983267 SNP variant also increases the risk of PC, breast cancer, bladder cancer, and other tumors. Interestingly, this SNP, which is located in the c-Myc enhancer region, [3] can regulate the Wnt signaling pathway. [44] In 2013, CCAT2 was found for the first time in microsatellite-stable CRC, located at 8q24, containing rs6983267 SNP.…”

“…Studies have shown that the abnormal expression of lncRNAs is strongly associated with the proliferation, migration, invasion, metastasis, cell cycle arrest, and other processes of various cancer cell types. [1][2][3] In addition, lncRNAs have great potential as diagnostic or prognostic biomarkers and can be therapeutic targets in a variety of human cancers. [4][5][6] Colon cancer-associated transcript 2 (CCAT2) is a 1752 bp lncRNA that was initially established to be an oncogene in colorectal cancer (CRC).…”

“…LncRNAs play a role in the modulating of the expression of genes at both the transcriptional and post-transcriptional levels, as well as participating in a variety of molecular regulatory mechanisms. Studies have shown that the abnormal expression of lncRNAs is strongly associated with the proliferation, migration, invasion, metastasis, cell cycle arrest, and other processes of various cancer cell types [1–3] . In addition, lncRNAs have great potential as diagnostic or prognostic biomarkers and can be therapeutic targets in a variety of human cancers [4–6] …”