MALAT1 lncRNA as a Therapeutic Target in Triple Negative Breast Cancer

在美国，每8名女性中就有1名会在一生中患上转移性乳腺癌， 占每年癌症诊断的近30%。乳腺癌的异质性使得 这种疾病的治疗是一个挑战，因为没有一种疗法对所有亚型都有效.近期 免疫疗法的发展，特别是检查点抑制，重振了创造 有助于提高对实体肿瘤的免疫反应的治疗方法。一种可能有帮助的新方法 提高乳腺癌免疫治疗反应的关键是高丰隆的抑制作用 非编码RNA(LncRNA)、转移相关肺腺癌转录本(MALAT1)。 MALAT1与肝癌、肾细胞癌、肺癌等癌症的进展有关 癌症，并已被证明在乳腺癌中上调了近四倍。目标锁定 通过使用反义寡核苷酸(ASO)，MALAT1成为可能。我们的实验室有 研究表明，在几个小鼠肿瘤来源的细胞系中，MALAT1的敲除也引起了增加 在胁迫标记p-eif2α和DNA损伤标记γH_2AX中。因此，靶向MALAT1可以 是一种有益的治疗方法，有助于提高对肿瘤细胞的免疫反应，从而产生肿瘤 微环境更容易受到检查点的抑制。

In the United States 1 in 8 women will develop metastatic breast cancer within their lifetime, accounting for nearly 30% of cancer diagnoses annually. The heterogeneity of breast cancer makes treatment of the disease a challenge, since no single therapy is effective for all subtypes. Recent developments in immunotherapy, notably checkpoint inhibition, has revitalized efforts to create therapies that help boost the immune response to solid tumors. A novel approach that may help improve immunotherapy response in breast cancer is the inhibition of highly abundant long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript (MALAT1). MALAT1, has been associated with the cancer progression of liver cancer, renal cell carcinoma, lung cancer and has been shown to be upregulated almost four-fold in breast cancer. Targeting of MALAT1 is made possible through the use of antisense oligonucleotides (ASO). Our laboratory has shown that knockdown of MALAT1 in several murine tumor derived cell lines also elicits an increase in the stress marker p-eIF2α, and DNA damage marker γH2aX. Thus, the targeting of MALAT1 may be a beneficial therapeutic to help increase the immune response to tumor cells, creating a tumor microenvironment more susceptible to checkpoint inhibition.