Lnc-OC1在卵巢癌和乳腺癌中的功能探究

卵巢癌和乳腺癌是两种严重危害女性健康的恶性肿瘤，对病人和社会经济都造成了巨大的负担。我国由于人口基数大，卵巢癌和乳腺癌的发病人数和死亡人数都高居世界前列，对其更为深入的研究将有助于相关肿瘤病人的诊断、治疗和预后。已有报道证明长链非编码RNA（LncRNA）在多种癌症中扮演着重要作用，我们的前期研究发现了一个在卵巢癌中具有功能的新的lncRNA，即LOC100288181，并将其命名为Lnc-OC1。在卵巢癌中，Lnc-OC1通过吸附miR-34a/miR-34c并抑制后者功能来进而促进卵巢癌细胞的增殖和迁移。本课题从一例中国女性卵巢癌病人腹水样本中分离并进行培养，得到原代培养细胞，通过免疫荧光、细胞流式分析鉴定其为癌细胞，并命名为Sample1。在此基础上进行了体外和体内一系列功能探究。结果表明，敲减Lnc-OC1显著抑制了Sample1细胞的增殖、迁移和浸润，促进了细胞凋亡。裸鼠体内成瘤实验表明，敲减Lnc-OC1显著抑制了肿瘤生长。耐药实验提示，卵巢癌中Lnc-OC1的表达和卡铂以及紫杉醇的耐药没有明显关系。我们也对Lnc-OC1在乳腺癌中的作用进行了初步探究。在乳腺癌细胞系MDA-MB-231进行Lnc-OC1敲减处理，发现细胞增殖、细胞成球能力和干细胞比例均受到抑制。上述结果表明，Lnc-OC1在卵巢癌和乳腺癌的发生过程中扮演着癌基因的角色，有可能成为一种潜在的诊断生物标志物和治疗靶点。

Ovarian cancer and breast cancer represent two kinds of malignant tumors which seriously threat women's health and bring a huge burden to the patients. Due to the large population in China, the patient numbers and deaths of ovarian and breast cancers are among the highest in the world. In-depth study of molecular mechanisms underlying ovarian and breast tumor development is helpful to the diagnosis, treatment, and prognosis of relevant tumor patients. It has been reported that long non-coding RNAs （lncRNAs） play an extremely important role in a wide-range of cancers. Our lab previously reported a novel LncRNA （LOC100288181, named as Lnc-OC1） in ovarian cancer. Lnc-OC1 promotes the proliferation and migration of ovarian cancer cells by sponging miR-34a/miR-34c. In this study, a primary culture named Sample1 was established from patient ascites and was used to test Lnc-OC1 function. Immunofluorescence staining and flow cytometry analysis demonstrated that the primary culture had the properties of epithelial cancer cells. A series of functional in vitro and in vivo experiments demonstrated that knockdown of Lnc-OC1 significantly inhibited cell proliferation, cell migration, and cell invasion, while promoting apoptosis. Tumorigenesis experiment showed that knockdown of Lnc-OC1 inhibited tumor growth. In addition, preliminary study suggests that Lnc-OC1 is not involved in the resistance of ovarian cancer cells to carboplatin or paclitaxel. In breast cancer cell line MDA-MB-231, knockdown of Lnc-OC1 could suppress the cell proliferation, cell spheroid capacity and stem cell ratio. These results suggest that Lnc-OC1 promotes the growth of ovarian and breast cancers, playing an oncogenic role.

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