lncRNA CCAT1 is a biomarker for the proliferation and drug resistance of esophageal cancer via the miR‐143/PLK1/BUBR1 axis

Abstract

Recent evidence indicates that long noncoding RNA colon cancer‐associated transcript‐1 (lncRNA CCAT1) is abundantly expressed in esophageal cancer and is closely related to the occurrence, development, invasion, metastasis, and drug resistance of this disease. However, the role and molecular mechanisms of CCAT1 in the cell proliferation and chemoresistance of esophageal cancer are largely unknown. The correlation between CCAT1 expression and drug resistance to cisplatin (CDDP) in esophageal squamous cell carcinoma (ESCC) cells was analyzed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) and quantitative real‐time polymerase chain reaction (qRT‐PCR) assays. CCAT1 knockdown and miR‐143 overexpression or inhibition were used to verify the effects on proliferation and drug resistance via MTT, western blotting, flow cytometry, and immunofluorescence assays. qRT‐PCR and western blotting were applied to detect the potential regulatory relationship among CCAT1, miR‐143, PLK1, and BUBR1. A xenograft tumor assay was performed to validate the role of CCAT1 in vivo. The expression of CCAT1 was positively correlated with drug resistance in several ESCC cell lines. CCAT1 knockdown and miR‐143 overexpression inhibited cell proliferation and CDDP drug resistance. Moreover, the downstream target of CCAT1 was found to be miR‐143, which can regulate the expression of PLK1 and BUBR1. In vivo assays showed that CCAT1 knockdown suppressed tumor growth and enhanced the sensitivity of tumors to CDDP in nude mice. Taken together, we discovered a novel mechanism by which CCAT1 promotes cell proliferation and enhances drug resistance by regulating the miR‐143/PLK1/BUBR1 signaling axis both in vitro and in vivo. Our findings further suggest that lncRNA CCAT1 may be a potential therapeutic target for overcoming chemoresistance in esophageal cancer.

Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis

“…5). CCAT1 seRNA is proved to be a significant biomarker in CRC, abundant studies have proved that it is also upregulated in different cancers, such as bladder cancer [73], esophageal cancer [74], cervical cancer [74], prostate cancer [103], and ovarian cancer [75]. In particular, squamous cell carcinoma (SCC) specific SE regions are cooperatively occupied with TP63 and SOX2 to boost CCAT1 seRNA transcription, CCAT1/TP63/SOX2 complex is bound to SE regions of epidermal growth factor receptor (EGFR) to promote EGFR transcription.…”

“…5). CRC-specific seRNA CCAT1-L has been proved to be overexpressed in various cancers including bladder, cervical and ovarian cancer, it promotes EMT activation, invasion and metastasis [73][74][75]. seRNA HCCL5 is considered as an SE-driven cytoplasmic lncRNA in HCC, and it accelerates EMT phenotype, invasion and metastasis in HCC cells by up-regulating Snail, Slug, ZEB1 and Twist1 expression [72].…”

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

“…A total of 10 hub genes, including AURKA, PLK1, TPX2, CDC6, FOXM1, TRIP13, RAD51AP1, ECT2, SPAG5, and CKS1B, were obtained from the PPI network of 93 overlapping DEGs in GSE92396, GSE17351, and GSE9982 datasets (Figure 1). It had been reported that AURKA [22], PLK1 [23], TPX2 [24], FOXM1 [25], TRIP13 [26], and CKS1B [27] were closely related to the development and progression of ESCC. However, the effects of CDC6, RAD51AP1, ECT2 and SPAG5 on the proliferation, apoptosis, invasion, migration and chemotherapy resistance in ESCC has rarely been reported.…”

Long Non-coding RNA Colon Cancer-Associated Transcript-1 Promotes Migration, Invasion, and Epithelial Mesenchymal Transition of Lung Adenocarcinoma by Suppressing miR-219-1

“…Long non-coding RNAs (lncRNAs) are a class of non-proteincoding transcripts longer than 200 nucleotides in length. Dysregulation of some lncRNAs promotes cellular processes related to cancer, including proliferation, invasion, metastasis, apoptosis, and drug resistance (Lu et al, 2017;Guan et al, 2019;Hu et al, 2019;Wang et al, 2019). Therefore, lncRNAs are considered a group of promising markers for predicting cancer prognosis and developing new therapeutic strategies.…”