Li Jingjing, Zhang Jing, Jin Liang, Deng Heran, Wu Jiannan
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China.
Anticancer Res. 2018 Jun;38(6):3427-3434. doi: 10.21873/anticanres.12611.
BACKGROUND/AIM: Persistent activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is an important mechanism in resistance of breast cancer to endocrine therapy. Although everolimus has potent inhibitory effects on the mTOR pathway, it has demonstrated only modest clinical activity as a single agent. Whether long noncoding (lnc) RNA is involved in everolimus resistance is unknown.
Cell viability, colony formation and cell proliferation experiments were used to measure the effects of long noncoding RNA N-acylsphingosine amidohydrolase 2B-2 (lnc-ASAH2B-2) knockdown in BT474 and MCF7 breast cancer cells.
lnc-ASAH2B-2 was up-regulated by everolimus in cells with and without serum, and reduction of lnc-ASAH2B-2 expression was able to inhibit proliferation of BT474 and MCF7 cells.
lnc-ASAH2B-2 was up-regulated after everolimus exposure and efficiently regulated breast cancer cell growth by activating the mTOR pathway, which may reduce the effect of everolimus, providing evidence that lnc-ASAH2B-2 might be a new therapeutic target for breast cancer.
背景/目的：磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素哺乳动物靶蛋白（mTOR）通路的持续激活是乳腺癌内分泌治疗耐药的重要机制。尽管依维莫司对mTOR通路有强大的抑制作用，但作为单一药物，其临床活性仅表现一般。长链非编码（lnc）RNA是否参与依维莫司耐药尚不清楚。
采用细胞活力、集落形成和细胞增殖实验来检测长链非编码RNA N-酰基鞘氨醇酰胺水解酶2B-2（lnc-ASAH2B-2）敲低对BT474和MCF7乳腺癌细胞的影响。
在有血清和无血清的细胞中，依维莫司均可上调lnc-ASAH2B-2的表达，降低lnc-ASAH2B-2的表达能够抑制BT474和MCF7细胞的增殖。
依维莫司作用后lnc-ASAH2B-2表达上调，并通过激活mTOR通路有效调控乳腺癌细胞生长，这可能会降低依维莫司的疗效，为lnc-ASAH2B-2可能成为乳腺癌新的治疗靶点提供了证据。
