Liu Haiying, Liu Jing, Zhao Guangzhang
Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.
Communicable Disease Control Division in Qingdao Chengyang District Center for Disease Control and Prevention, Qingdao, Shandong Province, China.
Arch Med Sci. 2019 Mar 11;16(5):1158-1165. doi: 10.5114/aoms.2019.83512. eCollection 2020.
Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are dysregulated in cancer cells and may be responsible for the development and progression of this disease. Herein, the role and therapeutic potential of aberrantly expressed lncRNA HOTAIR were investigated in cervical cancer.
The expression profile of the lncRNA HOTAIR was determined by quantitative RT-PCR. CCK-8 and colony formation assays were used for determination of cell viability. DAPI and annexin V/PI assays were used for detection of apoptosis. Wound healing and transwell assays were used to monitor cell migration and invasion.
The results showed that the expression of lncRNA HOTAIR was significantly ( < 0.01) upregulated (up to 4.1-fold) in cervical cancer cell lines. Silencing of lncRNA HOTAIR expression resulted in inhibition of the proliferation of the DoTc2 cervical cancer cells via induction of apoptotic cell death. HOTAIR silencing also resulted in decrease of the migration and the invasive properties of the cervical cancer cells. HOTAIR has been reported to interact with MAPK1 in cancer cells, and in this study MAPK1 was found to be overexpressed (up to 3.7-fold) in all the cervical cancer cells and silencing of HOTAIR inhibited the expression of MAPK1 in DoTc2 cervical cancer cells. Silencing of MAPK1 in DoTc2 cells also inhibited their proliferation and metastasis via induction of apoptosis. Co-transfection experiments showed that silencing of MAPK1 and lncRNA HOTAIR causes inhibition of DoTc2 cell growth synergistically.
These results indicate that lncRNA HOTAIR may prove to be an important therapeutic target for management of cervical cancer.
越来越多的证据表明，长链非编码RNA（lncRNA）在癌细胞中表达失调，可能与该疾病的发生和发展有关。在此，研究了异常表达的lncRNA HOTAIR在宫颈癌中的作用及治疗潜力。
通过定量RT-PCR测定lncRNA HOTAIR的表达谱。采用CCK-8和集落形成试验测定细胞活力。采用DAPI和膜联蛋白V/PI试验检测细胞凋亡。采用伤口愈合试验和Transwell试验监测细胞迁移和侵袭。
结果显示，lncRNA HOTAIR在宫颈癌细胞系中的表达显著上调（<0.01）（高达4.1倍）。lncRNA HOTAIR表达的沉默通过诱导凋亡性细胞死亡导致DoTc2宫颈癌细胞增殖受到抑制。HOTAIR沉默还导致宫颈癌细胞的迁移和侵袭特性降低。据报道，HOTAIR在癌细胞中与MAPK1相互作用，在本研究中发现MAPK1在所有宫颈癌细胞中均过表达（高达3.7倍），HOTAIR的沉默抑制了DoTc2宫颈癌细胞中MAPK1的表达。DoTc2细胞中MAPK1的沉默也通过诱导凋亡抑制了它们的增殖和转移。共转染实验表明，MAPK1和lncRNA HOTAIR的沉默协同抑制DoTc2细胞生长。
这些结果表明，lncRNA HOTAIR可能是宫颈癌治疗的一个重要靶点。
