Regulation of lnc-TLCD2-1 on Radiation Sensitivity of Colorectal Cancer and Comprehensive Analysis of Its Mechanism

Abstract

As is well known that colorectal cancer is the third most common cancer in the world, and radiation treatment plays a vital role in colorectal cancer therapy, but radiation resistance is a significant problem in the treatment of colorectal cancer. As an important member of the non-coding RNA family, long non-coding RNAs (lncRNAs) have been found that it plays a role in the occurrence and progression of colorectal cancer in recent years. However, little is known about the effect of lncRNA on colorectal cancer sensitivity to radiotherapy. We found that lnc-TLCD2-1 was significantly differentially expressed in radiation-tolerant CCL244 cell lines and radiation-sensitive HCT116 cell lines, suggesting that lnc-TLCD2-1 may regulate the radiosensitivity of colorectal cancer, and the relevant underlying mechanism was investigated. Cell clone formation assay, flow cytometry, and cell counting kit 8 (CCK8) were used to detect radiation sensitivity, apoptosis, and proliferation of colorectal cancer cells, respectively; Quantitative real-time PCR and western blot were used to detect the expression of genes; the direct interaction between lnc-TLCD2-1 and hsa-miR-193a-5p was verified by dual luciferase reporter assays; GEPIA, Starbase, TIMER and DAVID were used to complete expression of lnc-TLCD2-1, miR-193a-5p,YY1 and NF-кB-P65 in colorectal cancer, correlation, immune cell infiltration, GO and KEGG enrichment analysis. Clinical prognostic analysis data were obtained from GSE17536 dataset. After radiotherapy for HCT116, the expression of lnc-TLCD2-1 was increased, and the expression of hsa-miR-193a-5p was significantly decreased, while that of CCL244 was the opposite, and the change range of lnc-TLCD2-1 was relatively small. HCT116 with overexpression of lnc-TLCD2-1 after radiation treatment, the number of cell colonies significantly increased, and cell apoptosis decreased compared with the negative control group. The cell colonies and apoptosis of CCL244 with disturbed expression of lnc-TLCD2-1 were opposite to those of HCT116. Lnc-TLCD2-1 can regulate the expression of YY1/NF-кB-P65 by targeting miR-193a-5p. Lnc-TLCD2-1 can promote the proliferation of colorectal cancer. High expression of lnc-TLCD2-1 independently predicted a shorter survival. Lnc-TLCD2-1 is associated with radiation resistance and short survival in colorectal cancer patients. In addition, Lnc-TLCD2-1 can promote the proliferation of colorectal cancer. Our study provides a scientific basis for targeting lnc-TLCD2-1 in colorectal cancer radiation resistance interventions and selection of prognostic biomarker.

Integrated Bioinformatics Analysis of Serine Racemase as an Independent Prognostic Biomarker in Endometrial Cancer

“…Our study discovered that hsa-miR-193a-5p and hsa-miR-1301-3p could be potential miRNAs upstream of SRR. Previous studies have suggested that hsa-miR-193a-5p may play a role in the invasiveness of malignant pleural mesothelioma cells ( Jotatsu et al, 2020 ), and a significant reduction in hsa-miR-193a-5p level was observed after irradiation of the colorectal cancer cell line HCT116 ( Yu et al, 2021 ). Similarly, Pu et al (2016) reported that hsa-miR-193a-5p contributes to osteosarcoma metastasis by suppressing SRR expression.…”

NORAD-sponged miR-378c alleviates malignant behaviors of stomach adenocarcinoma via targeting NRP1

“…Long non-coding RNAs (LncRNAs) contain more than 200 nucleotides in length [ 8 ], and function as regulators in various biological behaviors, such as cell proliferation [ 9 ], migration [ 10 ], invasion [ 11 ] and EMT process [ 12 ]. LncRNAs like ABHD11-AS1 [ 9 ], TLCD2-1 [ 13 ] and HOTTIP [ 14 ] were highly correlated with progression of multiple cancers through activating or inhibiting gene expression. More specifically, Lu et al ascertained that LncRNA NEAT1 upregulated ROCK1 through sponging miR-148b-3p to hinder retinoblastoma growth and metastasis [ 15 ].…”

The Roles of Non-Coding RNAs in Radiotherapy of Gastrointestinal Carcinoma

“…Lnc-UCA1 interfered with the radiosensitivity of CRC cells by boosting EMT and G2/M arrest and suppressing irradiation-induced apoptosis ( Yang et al, 2018 ). Yu et al (2021) reported that lnc-TLCD2-1 was downregulated in CRC tissues and radiosensitive cell lines. lnc-TLCD2-1 induced the radioresistant status of CRC cells by elevating cell viability and repressing irradiation-induced apoptosis.…”

“…miR-183-5p abated the response of CRC cells to RT by directly binding to ATG5 ( Zheng et al, 2019 ). Lnc-TLCD2-1 activated the NF-кB pathway to cause radioresistance in CRC cells via regulating YY1 by targeting miR-193a-5p ( Yu et al, 2021 ). Increased miR-106b levels downregulated PTEN and p21 expression and subsequently enhanced radioresistance in CRC cells ( Zheng et al, 2015 ).…”

“… Xiao et al (2020) revealed that the high lnc-TRPM2-AS expression was accurately forecasted advanced clinicopathological characteristics and significantly correlated to the shorter OS and recurrence-free survival (RFS) of GC patients. Meanwhile, high lnc-TLCD2-1 expression predicted worse OS and disease-specific survival of CRC patients from the GSE17536 dataset ( Yu et al, 2021 ). For CRC patients with high miR-183-5p expression, the OS was worse ( Zheng et al, 2019 ).…”