The prognostic significance of protein arginine methyltransferase 6 expression in colon cancer

Abstract

Protein arginine methylation is involved in cellular differentiation and proliferation. Recently, aberrant expression of protein arginine methyltransferases, which are responsible for the methylation reaction, has been reported in various types of cancer. However, there is no clear evidence regarding the prognostic value of abnormal PRMT6 expression in colorectal cancer or the effect of PRMT6 regulation on CRC cells. We investigated the expression patterns of PRMT6 in patients with stage II and III CRC. We detected nuclear expression of PRMT6 in 23.7% of carcinoma samples by immunohistochemistry. Among the clinicopathological parameters, the ratio of poorly differentiated cancer cells was approximately two-fold higher in patients with PRMT6-positive disease than in those with PRMT6-negative disease (p = 0.002). Patients with PRMT6-positive CRC had a shorter disease-free survival than those with PRMT6-negative CRC in both univariate and multivariate analyses (p = 0.018 and p = 0.035, respectively). siRNA-mediated inhibition of PRMT6 expression in CRC cells induced p21WAF1/CIP1 overexpression and suppressed cell growth and colony-forming ability. Concomitantly, apoptosis was induced in PRMT6-suppressed CRC cells. These data suggest that PRMT6 can serve as a biomarker for unfavorable prognosis and as a therapeutic target in CRC.

Proteome-wide identification of arginine methylation in colorectal cancer tissues from patients

“…Observations from clinical samples showed that 75% of colorectal cancers had CARM1 overexpression [18]. In our recent study, patients with PRMT6-positive CRC by immunohistochemistry had shorter disease-free survival than those with PRMT6-negative CRC in both univariate and multivariate analyses [19]. All these studies strongly suggest that CRC tissues from patients might be suitable in vivo source for identification of arginine methylation.…”

“…Based on the previous studies [16,18,19], we first examined the presence of three type I PRMTs, namely PRMT1, PRMT4 and PRMT6, by Western immunoblot using CRC tissue extracts from patients with stage II and III as well as DLD1 and HCT116 cell lysates. As shown in Fig.…”

“…Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a leading cause of cancer death worldwide [15]. Previously, overexpression of three major type I PRMTs including PRMT1 [16], PRMT4 [17,18], and PRMT6 [19] was observed in CRC. The expression of one of splice variants of PRMT1 is significantly higher in colon cancer tissue compared with normal tissue.…”

Significant association of PRMT6 hypomethylation with colorectal cancer

“…The p21 plays an important role in the development and progression of cancer, and hypermethylation of p21 leads to downregulation of p21 gene expression . Downregulated expression of PRMT6 in CRC cells can induce p21 overexpression and inhibit cell growth and colony formation capacity . PRMT6 is often found to be overexpressed in cancers, including CRC, bladder cancer, lung cancer, prostate cancer, and breast cancer .…”

“…Downregulated expression of PRMT6 in CRC cells can induce p21 overexpression and inhibit cell growth and colony formation capacity . PRMT6 is often found to be overexpressed in cancers, including CRC, bladder cancer, lung cancer, prostate cancer, and breast cancer . In the present study, we found PRMT6 hypomethylation was significantly associated with CRC.…”