权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Investigation of control of pRB and cell transformation by a long non-coding RNA

长非编码RNA对pRB和细胞转化的控制的研究

基本信息

批准号：
MR/P00041X/1
负责人：
Peter Adams
金额：
$ 71.02万
依托单位：
University of Glasgow
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FP00041X%2F1
关键词：
Investigation control pRB cell transformation

项目摘要

Melanoma is a cancer of pigment producing cells called melanocytes, most often in the skin. Melanoma is the 6th most common cancer in the UK and advanced melanoma still has a very poor prognosis (www.cancerresearchuk.org). In 2016, approximately 13,300 people in the UK will be diagnosed with melanoma. At current rates, approximately 2,100 of these will die from the disease. Thus, there is a need for a better understanding of this disease to ultimately facilitate better cures. Remarkably, most people carry the earliest detectable skin lesions as precursors to melanoma, in the form of benign human nevi or moles. Moles typically carry one of the genetic alterations known to drive melanoma, either an activated NRAS or BRAF oncogene. However, moles only very rarely progress to melanoma because the melanocytes harboring the oncogene are prevented from proliferating by a process called cell senescence. Consequently, a better understanding of senescence in melanocytes can aid in understanding the body's natural defences to melanoma. Eventually, this might be harnessed in therapies. One molecule critical for cell senescence and preventing tumor formation is the retinoblastoma tumor suppressor (pRB). As its names suggests, this molecule was first discovered through its ability to prevent retinoblastoma, a cancer of the eye. However, pRB also contributes to suppression of melanoma and many other cancers, in part through activation of cell senescence. Thus, it is important to understand control of pRB. We have discovered another molecule, called LNC98, which is required for cells to produce pRB. This in turn suggests that LNC98 might suppress melanoma formation. Consistent with this idea, we have found that LNC98 is inactivated in some human melanomas, perhaps accounting for their unrestrained growth and proliferation. In this study, we will investigate the molecular mechanism by which LNC98 promotes production of pRB in cells and investigate the role of LNC98 in suppression of melanoma. Completion of these studies should provide new therapeutic avenues to manage and treat melanoma.

黑色素瘤是一种色素产生细胞称为黑色素细胞的癌症，最常见于皮肤。黑色素瘤是英国第6大最常见的癌症，晚期黑色素瘤的预后仍然非常差（www.cancerresearchuk.org）。2016年，英国约有13，300人被诊断患有黑色素瘤。按照目前的速度，其中约有2,100人将死于这种疾病。因此，有必要更好地了解这种疾病，以最终促进更好的治疗。值得注意的是，大多数人携带最早可检测到的皮肤病变，作为黑色素瘤的前兆，以良性人类痣或痣的形式存在。鼹鼠通常携带一种已知的驱动黑色素瘤的基因改变，无论是激活的NRAS还是BRAF癌基因。然而，痣很少发展为黑色素瘤，因为携带癌基因的黑色素细胞被称为细胞衰老的过程阻止增殖。因此，更好地了解黑素细胞的衰老可以帮助了解身体对黑色素瘤的天然防御。最终，这可能会被用于治疗。一种对细胞衰老和防止肿瘤形成至关重要的分子是视网膜母细胞瘤肿瘤抑制因子（pRB）。正如它的名字所暗示的那样，这种分子最初是通过其预防视网膜母细胞瘤（一种眼睛癌症）的能力而被发现的。然而，pRB也有助于抑制黑色素瘤和许多其他癌症，部分通过激活细胞衰老。因此，理解pRB的控制是重要的。我们发现了另一种分子，称为LNC 98，它是细胞产生pRB所必需的。这反过来表明LNC 98可能抑制黑色素瘤形成。与这一想法一致，我们发现LNC 98在一些人黑色素瘤中失活，这可能是它们无限制生长和增殖的原因。在这项研究中，我们将研究LNC 98促进细胞中pRB产生的分子机制，并研究LNC 98在抑制黑色素瘤中的作用。这些研究的完成将为管理和治疗黑色素瘤提供新的治疗途径。