Dysregulation of long non-coding RNA profiles in human colorectal cancer and its association with overall survival

Abstract

Abstract. Long non-coding RNAs (lncRNAs) emerged as key regulators of diverse roles during colorectal cancer (CRC) carcinogenesis, but their specific function still remains to be explored. The present study aimed to re-annotate the Affymetrix Human Exon 1.0 ST Array for defining differential lncRNAs in CRC. Their prognostic relevance was also developed for screening key regulators in CRC. The CRC datasets E-GEOD-31737, E-MATB-829, Affymetrix colon cancer dataset and E-GEOD-24550 were re-purposed for searching differential lncRNAs and exploring their association with overall survival (OS). The identified lncRNAs were validated in CRC tissues or cell lines. As a result, 462, 286 and 166 differential lncRNAs were identified, respectively, in three predictive datasets. Among them, 48 lncRNAs were commonly observed to exhibit differential expression in the three datasets. Notably, the overexpression of family with sequence similarity 83 member H (FAM83H)-antisense (AS) 1 (P=0.038) and VPS9 domain containing 1 (VPS9D1)-AS1 (P=0.020) indicated shorter OS time than lower expression. The overexpression of FAM83H-AS1 (P=0.033) and VPS9D1-AS1 (P=0.011) was validated in cancerous tissues. Thus, FAM83H-AS1 and VPS9D1-AS1 may potentially enhance carcinogenesis or may be developed as prognostic biomarkers for CRC. In conclusion, a total of 48 CRC-related lncRNAs were identified, the majority of which were confirmed to exhibit dysregulation. FAM83H-AS1 and VPS9D1-AS1 could have a potential use as prognostic biomarkers for CRC patients. IntroductionColorectal cancer (CRC) is a malignant disease that originates from colorectal epithelial cells (1), and is one of the most commonly diagnosed malignancies in the world (2). Genetic events such as rare or high-penetrance variants in the CRC susceptibility genes and DNA mismatch repair genes have been demonstrated to be important in the etiology of both sporadic and familial CRC (3). However, the carcinogenic mechanisms can only be explained in <6% of all CRC cases (3). Therefore, there are still numerous genetic events associated with dysregulation or mutations in CRC patients that remain to be determined.Long non-coding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides without coding potential to be translated into proteins (4). Numerous studies have revealed that lncRNAs were frequently dysregulated in various diseases and had multiple functions in a wide range of pathological processes, including apoptosis, proliferation and invasion-metastasis of malignant tumors (5,6). For instance, colorectal cancer associated transcript 2 was identified by Ling et al as a lncRNA mapping to 8q24 that promoted metastatic progression in CRC (7). Another lncRNA, homeobox transcript antisense intergenic RNA (HOTAIR) has been determined to exhibit higher levels in the plasma of CRC patients than in healthy controls, and its overexpression predicted unfavorable prognosis (8). The association between prognosis of CRC patients and expression of prostate cancer associated transcript 1...

Identification of lncRNAs associated with early stage breast cancer and their prognostic implications

“…FAM83H-AS1 was consistently over expressed in breast tumor samples and overall survival analysis of TCGA data sets showed poor prognosis of the up regulated group which are in agreement with other studies in breast, colorectal and lung cancer (Lu et al, 2018;Yang et al, 2016a;Yang et al, 2016c;Zhang et al, 2017). Functional studies have demonstrated that knock-down of FAM83H-AS1 proliferative potential through MET/EGFR signaling in lung adenocarcinoma and NOTCH1 signaling pathway in colorectal cancer.…”

Long non-coding RNA MYU promotes prostate cancer proliferation by mediating the miR-184/c-Myc axis

“…MYU is expressed in various tumors with a broad spectrum. MYU has been reported to regulate CRC based on its annotated sequence (14,15). However, its future application may be limited due to the lack of an accurate transcript.…”

“…A c-Myc-upregulated lncRNA MYU (ENSG00000261373) has been reported to exert an oncogenic effect in colorectal cancer (CRC) (14,15), but functions as a tumor-suppressor gene in gastric cancer (GC) (16). A recent study suggests that MYU as a target for Wnt/c-Myc signaling can promote cell cycle progression by stabilizing CDK6 expression via associating with hnRNP-K (14).…”

The clinical prognostic value of lncRNA FAM83H-AS1 in cancer patients: a meta-analysis

“…The 14 studies contained 2818 patients from three countries including China, United States and Iran. We mainly analyzed nine different types of tumors, including pancreatic ductal adenocarcinoma [13], gastric cancer [7,14,15], ovarian cancer [8,16], glioma [9], colorectal carcinoma [17,18], bladder cancer [10], hepatocellular carcinoma [6], breast cancer [19], and lung cancer [20]. The expression of FAM83H-AS1 was detected by quantitative real-time fluorescent PCR in all studies.…”