UHRF1 expression is upregulated and associated with cellular proliferation in colorectal cancer

Abstract

Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) binds to methylated promoters of a number of tumor-suppressor genes, including p16INK4A and p14ARF, by forming complexes with DNA methyltransferases and HDAC1, resulting in the induction of carcinogenesis. Altered UHRF1 expression has been demonstrated in various types of cancers. Previous reports indicate that UHRF1 expression is regulated by E2F-1 expression. We investigated UHRF1 expression using immunohistochemical staining in 231 colorectal cancer and 40 adenoma specimens, analyzed the relationship between UHRF1 expression and clinicopathological findings and the association between UHRF1 and E2F-1 expression. To better understand the biological function of UHRF1 in colorectal cancer, knockdown of UHRF1 expression was performed using siRNA methods. High UHRF1 expression was observed in 152 of 231 (65.8%) colorectal cancer patients, and was detected in 35 of 40 adenoma specimens samples (87.5%). UHRF1 staining was detected in the nucleus of cancer cells, while it was not detected in colonic normal mucosa. High UHRF1 expression was significantly observed in right compared with left hemicolon cancer (p=0.008). Moreover, high UHRF1 expression tended to be associated with depth of invasion (p=0.051). UHRF1 expression was significantly associated with E2F-1 expression (p<0.0001). Knockdown of UHRF1 expression suppressed cellular growth in colon cancer cell lines, HCT116 and SW620. In conclusion, we demonstrated that UHRF1 expression was upregulated in approximately two-thirds of colorectal cancer specimens and was particularly expressed in right compared with left hemicolon cancer. Moreover, knockdown of UHRF1 expression induced growth inhibition in colon cancer cell lines. UHRF1 may be involved in cellular proliferation and molecular pathogenesis of colorectal cancer in the right hemicolon.

Revealing ETC-1922159 Affected Unknown 3<em>^rd</em> order WNT10B-X-X Combinations, in Silico

“…Wang et al 71 also show that UHRF1 is upregulated in colorectal cancer case and facilitates in cell proliferation and metastasis via suppression of p16 nk4 . Similar findings have been made in 72 , 73 & 74 . Consistent with these, the UHRF1 was down regulated in cancer cells, on the treatment with ETC-1922159.…”

Ubiquitin E3 ligase UHRF1 regulates p53 ubiquitination and p53-dependent cell apoptosis in clear cell Renal Cell Carcinoma

“…Knockdown of UHRF1 expression in cancer cells significantly suppressed cell growth, indicating that UHRF1 was essential for progression of cancers [13]. Collectively, UHRF1 may serve as an attractive biomarker and therapeutic target for cancer treatment [3,14,15].…”

UHRF1: The key regulator of epigenetics and molecular target for cancer therapeutics

“…3 Structurally, it is composed of five functionally recognizable domains which allow it to interact with several protein and nonprotein partners to actively regulate DNA methylation, chromatin modifications, cellular proliferation and DNA repair. 4 Aberrations in UHRF1 expression correlate with aggressiveness of many different human malignancies such as laryngeal squamous cell carcinoma, 5 breast cancer, 6 lung cancer, 7 hepatocellular carcinoma, 8 gastric cancer, 9 renal cell carcinoma, 10 cervical cancer, 11 bladder cancer, 12 colorectal cancer 13 and osteosarcoma. 14 Presence of high circulatory levels of UHRF1 DNA in blood samples of breast and gastric cancer patients underlined its importance to act as an independent diagnostic and prognostic marker.…”