Downregulation of lncRNA CCAT1 enhances 5-fluorouracil sensitivity in human colon cancer cells

Abstract

Background The purpose of this study was to determine the aberrant expression of the long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) in 5-fluorouracil-resistant colonic neoplasm cells and to elucidate its effects on the 5-fluorouracil sensitivity of human colonic neoplasm cells. The aberrant expression of lncRNAs in normal tissues and colonic neoplasm tissues was detected by microarray assay. qRT-PCR analysis was performed to assess CCAT1 expression levels in colonic neoplasm cell lines and corresponding normal tissues. After constructing the 5-FU-resistant cell lines and validating the resistance by measuring the IC 50 value, the CCAT1 expression levels in parental and artificially resistant cell lines were determined by qRT-PCR. Transfection was used to modulate the expression of CCAT1. Cell proliferation and apoptosis were then detected by CCK-8 and flow cytometry, respectively. Results CCAT1 in colon cancer tissues was higher than that in noncancer tissues, and the levels of CCAT1 in HCT 116, SW1417, HT-29, and KM12 cell lines were higher than those in the human normal colon epithelial NCM460 cell line. Moreover, the expression levels of CCAT1 were high in HCT 116/5-FU and HT-29/5-FU cell lines, whose apoptosis rates induced by 5-FU were lower than those in corresponding parental cells. The results of qRT-PCR and CCK-8 assay showed that enhancement of lncRNA CCAT1 expression levels in HCT 116 and HT-29 cell lines increased their IC 50 of 5-FU and decreased their apoptosis rates. Meanwhile, siRNA-CCAT1 effectively inhibited the expression of CCAT1 and enhanced the 5-FU-sensitivity of HCT 116/5-FU and HT-29/5-FU, in which apoptosis rates were increased at the same time. Conclusions Downregulation of CCAT1 effectively reversed the resistance of HCT 116/5-FU and HT-29/5-FU cells to 5-FU chemotherapeutic, opening a new avenue in colon cancer therapy.

RETRACTED ARTICLE: SOX2 Regulates lncRNA CCAT1/MicroRNA-185-3p/FOXP3 Axis to Affect the Proliferation and Self-Renewal of Cervical Cancer Stem Cells

“…Long non-coding RNAs (lncRNAs) are a class of RNA molecules with 200 nucleotides in length [9]. LncRNA colon cancerassociated transcript-1 (CCAT1) is located on human chromosome 8q24.21 and considered as a "hot spot" that results in genetic mutations in colon cancer [10]. A study has reported that CCAT1 accelerates cell proliferation and invasion of CC [11].…”

Long Non-coding RNA CCAT1 Acts as an Oncogene and Promotes Sunitinib Resistance in Renal Cell Carcinoma

“…For instance, CCAT1 triggered cisplatin resistance via sponging miR-130a-3p in lung cancer (27). Deregulation of CCAT1 impeded 5-FU resistance of colon cancer (28). The current evidence broadened the knowledge of lncRNAs and sunitinib resistance, suggesting that CCAT1 served as a pivotal oncogene in antagonizing targeted therapy.…”

Dynamic immunity gene and lncRNA regulatory cooperative pairs revealed prognostic signatures in the development of colon cancer

“…In the past few years, a number of studies have successfully characterized the roles of lncRNAs based on the general assumption that lncRNAs are key regulators of biological processes in many kinds of cancers. Although many studies have been carried out to characterize the complex and multiple functions of lncRNAs including cell growth [16], apoptosis [17], autophagy, epithelial mesenchymal transformation [18] and so on, little is known about the roles of lncRNAs in immune regulations for colon cancer.…”