Genetic variation of long non-coding RNA TINCR contribute to the susceptibility and progression of colorectal cancer

Abstract

Colorectal cancer (CRC) accounts for the leading causes of cancer-related morbidity and mortality. However, a large part of heritable factors are warranted to be explored. Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and progression. Herein, we explored effect of genetic variants of Tissue differentiation-inducing non-protein coding RNA (TINCR), a key lncRNA required for somatic tissue differentiation and tumor progression, on risk and progression of CRC. Three tagSNPs, including rs2288947, rs8105637, and rs12610531, were evaluated in in a two-stage, case-control study. Two SNPs, rs2288947 and rs8105637, were significantly associated with susceptibility of CRC in both stages. When pooled together, the allele G was significantly associated with 23% decreased risk of CRC (OR=0.77; 95% CI=0.67-0.88; P value = 1.2×10−4)for SNP rs2288947. While for SNP rs8105637, the allele A was significantly associated with 22% increased risk of CRC (OR=1.22; 95% CI=1.09-1.37; P value = 6.2×10−4). The two SNPs were also statistically associated with occurrence of lymph node metastasis of CRC. The carriers of allele G are less likely to get lymph node metastasis (OR=0.77; 95% CI=0.63-0.94; P value = 0.011) for rs2288947, and the carriers of allele A are more likely to get lymph node metastasis (OR=1.22; 95% CI=1.03-1.43; P value = 0.019) for rs8105637. These results suggest that lncRNA TINCR polymorphisms may be implicated in the development and progression of CRC.

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

“…Since their discoveries, a large amount of lncRNA has been found being dysregulated in a range of cancers [5]. In addition, they are being identified and characterized for serial steps of cancer development, including tumor initiation, growth, and metastasis [6]. Maternally expressed gene 3 (MEG3), a lncRNA that has attracted much research interest, is aberrantly expressed in several human cancers including ovarian cancer [7], gastric cancer [8], colorectal cancer [9], cervical cancer [10], and malignant glioma [11].…”

Association between the rs2288947 polymorphism of the lncRNA TINCR gene and the risk of recurrent miscarriage in a Southern Chinese population

“…A study by Ma et al found that SNPs of the lncRNA TINCR were significantly associated with decreased gastric cancer susceptibility by decreasing its gene expression levels. Moreover, a study by Zheng et al found that lncRNA TINCR polymorphisms were associated with the progression of colorectal cancer, and SNP rs2288947 may be a biomarker with the occurrence and progression of colorectal cancer. In our case‐control study with 248 patients with recurrent miscarriage and 392 healthy controls from the Southern Chinese population, we did not observe a significant relationship between the TINCR gene rs2288947 A > G polymorphism and the recurrent abortion susceptibility of women in Southern China.…”

“…[15][16][17][18] Recently, studies have found that genetic variation in TINCR was associated with a variety of diseases, such as the SNP rs2288947, which contributed to the susceptibility and progression of colorectal cancer and susceptibility to gastric cancer. 19,20 Furthermore, studies have found that some genes that regulate cell proliferation, invasion, and migration are associated with susceptibility to miscarriage; for example, H19 and p53 gene polymorphisms. 8,21 These studies suggest that TINCR gene polymorphisms may be associated with recurrent miscarriage.…”

Rs2262251 in lncRNA RP11‐462G12.2 is associated with nonsyndromic cleft lip with/without cleft palate

“…LncRNAs are the largest subclass of noncoding transcripts in humans and extensively participate in cellular processes to regulate gene expression on the transcriptional, epigenetic, and posttranscriptional levels (Hung & Chang, 2010;Mercer & Mattick, 2013;Yoon, Abdelmohsen, & Gorospe, 2013). SNPs in exons of lncRNAs may change the structure of their host gene and affect both gene expression and function (Chang et al, 2013); moreover, such SNPs are involved in various types of human diseases (Du et al, 2015;Wu et al, 2013;Zheng et al, 2016Zheng et al, , 2017. For instance, exonic SNPs in LINC00673 and LINC-TINCR were associated with the development of pancreatic (Zheng et al, 2016) and colorectal (Zheng et al, 2017) cancer, respectively.…”

“…SNPs in exons of lncRNAs may change the structure of their host gene and affect both gene expression and function (Chang et al, 2013); moreover, such SNPs are involved in various types of human diseases (Du et al, 2015;Wu et al, 2013;Zheng et al, 2016Zheng et al, , 2017. For instance, exonic SNPs in LINC00673 and LINC-TINCR were associated with the development of pancreatic (Zheng et al, 2016) and colorectal (Zheng et al, 2017) cancer, respectively. However, the roles of exonic SNPs in the development of NSCL/P have not been investigated.…”