Association of lncRNA‑p53 regulatory network (lincRNA‑p21, lincRNA‑ROR and MALAT1) and p53 with the clinicopathological features of colorectal primary lesions and tumors

Abstract

Colorectal cancer (CRC) is a common intestinal cancer with a high mortality rate. Early detection of this type of cancer is fundamental to the prevention of the disease, which results in improved survival rates. In the human colon tissue, transition from normal epithelium to adenoma is considered to be caused by unknown molecular incidents occurring over 5-10 years. The detection of CRC has proved problematic when in the early stages of disease. In addition, identifying suitable biomarkers for the detection of CRC progress in patients remains one of the most significant challenges. Long non-coding RNAs have been demonstrated to contribute to the promotion of CRC. The aim of the present study was to investigate the clinical and biological significance of long intergenic non-coding (linc)RNA-p21, lincRNA-regulator of reprogramming (ROR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the colon tumor and polyp tissue, and the association that these have with the expression of p53 at the mRNA level. Neoplastic and paired adjacent normal tissue samples were obtained from 72 patients (46 polyps and 26 tumors). Reverse transcription-quantitative PCR was performed to determine the relative fold changes in the expression of lincRNA-p21, lincRNA-RoR, MALAT1 and p53 in the samples. A significant association was observed between the levels of MALAT1 and p53 in neoplasm tissues (R=0.073; P<0.05). The relative expression of the MALAT1 gene revealed a statistically significant difference between the different polyp types and number of polyps (P=0.0028 and 0.022, respectively). Adjuvant therapy in patients with tumors revealed an association between the levels of lincRNA-ROR and lincRNA-p21 expression (P=0.015 and 0.038, respectively). MALAT1 may be selected as an early detection biomarker for CRC. Furthermore, lincRNA-ROR and lincRNA-p21 may serve as prognostic and therapeutic biomarkers in patients with CRC.

LincRNA-p21 Levels Relates to Survival and Post-Operative Radiotherapy Benefit in Rectal Cancer Patients

“…However, no association with neither OS nor metastasis-free survival were found, maybe due to the reduced number of patients. However, in a more recent study [ 24 ] in 66 CRC patients, no significant differences were observed between tumor and adjacent normal tissue and lincRNA-p21 levels, but they found using ROC curve analysis that lincRNA-p21 could have an impact as diagnostic marker (AUC tumor versus normal tissue of 0.796). The prognosis impact was not studied in that work.…”

“…The prognosis impact was not studied in that work. Since lincRNA-p21 have been described as key element in the TP53 pathway, both papers studied the association with TP53 in patient samples, analyzing the correlation with TP53 mutational status [ 22 ] or the correlation with p53 mRNA levels [ 24 ]. However, no significant correlations with TP53 were observed in both papers.…”

Lincp21-RNA as Predictive Response Marker for Preoperative Chemoradiotherapy in Rectal Cancer

“…Nonetheless, these results are not comparable with the present work since our correlation was obtained in tumor tissue isolated prior to adjuvant CRT treatment administration. Moreover, the two previous references focused on the potential role of lincRNA-p21 and radiotherapy response in relation to its role in the p53 pathway [ 21 , 30 , 31 , 32 ]; nonetheless, we cannot ignore that rectal cancer patients included in the cohort also received 5-fluorouracil. Lee and colleagues analyzed the pattern of lncRNAs in 5-fluorouracil-resistant colon cancer cell lines and observed that lincRNA-p21 was significantly upregulated in SNU-C5 5-FU-resistant cells compared to its parental cell line [ 33 ].…”

Evaluation of AK023391 lncRNA and FOXO3a Genes’ Expression in Tissues from Iranian Gastric Cancer Patients Compared with Healthy Tissues and Their Relationship with Clinicopathological Features

“…It has been previously shown that lncRNAs contribute to GC development through several signaling pathways such as AKT and MAPK (23). Furthermore, interactions between lncRNAs and their target genes seem to affect pathogenic mechanisms in GC (24). Indeed, lncRNAs have a wide range of functions, including tumor growth sup-pression and oncogenesis regulation, and can act through a number of pathways (25).…”