The 9p21 locus: A potential therapeutic target and prognostic marker in breast cancer

Abstract

Breast cancer is an important cause of cancer related mortality in women. Despite extensive efforts to identify valid biomarkers for risk stratification, there are relatively few with proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to breast cancer. Recent genome-wide-association-studies and gene expression analysis have demonstrated that a locus on chromosome 9p21, which contains three genes; CDKN2B (encoding p15ink4b), CDKN2A (encoding p16ink4a and p14ARF) and the 3' end of CDKN2BAS (an antisense noncoding RNA in the INK4 locus [ANRIL]) are associated with an increased risk of this malignancy. ANRIL has a post transcriptional modulatory activity, which has been shown to perturb the expression of nearby genes and may play an important role in coordinating tissue remodeling through regulation of cell proliferation, apoptosis, aging, extra-cellular matrix remodeling, and inflammatory response. However, the role of ANRIL is not well understood in breast cancer. Hypermethylation of the p14 and p16 genes is found in some tumor types. Nevertheless, further studies are necessary to confirm the clinical utility of these putative markers in risk stratification, or assessing prognosis. In this review, we have summarized the prognostic and therapeutic potential of the p14 and p16 genes in patients with breast cancer.

Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids

“…The observation that Suz12 deficiency in normal mammary cells leads to de-repression of cdkn2a , paralleling that seen with loss of Ezh2 [ 32 ], would predict that loss of PRC2 function in breast cancer would result in decreased tumor proliferation via up-regulation of p16 Ink4a and p14Arf expression. However, if this locus is perturbed, as is seen in many breast cancers [ 33 ], then loss of Ezh2 might have quite different consequences. Further work will be required to determine if loss rather than overexpression of PRC2 contributes to tumor progression in other cellular contexts.…”

RETRACTED ARTICLE: Inhibition of ZEB1-AS1 confers cisplatin sensitivity in breast cancer by promoting microRNA-129-5p-dependent ZEB1 downregulation

“…Breast cancer is a common malignancy associated with high mortality rates among women due to a limitation in the clinically proven treatment regimens [1]. Breast cancer is correlated with various extrinsic and intrinsic risk factors, such as environmental and genetic factor, tumor history in direct relatives, late menopause, early menarche and age more than 40 [2].…”

LncRNA CDKN2BAS predicts poor prognosis in patients with hepatocellular carcinoma and promotes metastasis via the miR-153-5p/ARHGAP18 signaling axis

“…In the past few years, the importance of lncRNAs in the metastasis of HCC has been documented [16-19]. CDKN2BAS, a member of the lncRNA family, plays important roles in cell proliferation, apoptosis, and extra-cellular matrix remodeling [20,21]. CDKN2BAS expression has been reported to be associated with susceptibility to several important human diseases, such as coronary artery disease and diabetes [20].…”