Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Department of Gynecology, Fufeng County People's Hospital, Baoji 722299, China.
Biomed Pharmacother. 2019 Sep;117:108726. doi: 10.1016/j.biopha.2019.108726. Epub 2019 Jun 12.
Cervical cancer is the second most common gynecological malignancy, and it remains a leading cause of tumor-related death among female in the world. Long non-coding RNAs (lncRNAs) have been indicated to play essential roles in tumorigenesis, and the lncRNA colorectal neoplasia differentially expressed (CRNDE) is increased in several tumors. Nevertheless, little is known about the effects of lncRNA CRNDE on human cervical cancer. The aim of the study was to explore the clinical significance of lncRNA CRNDE expression in human cervical cancer. Our results indicated that CRNDE expression was increased in cervical cancer tissues and several cervical cancer cell lines. Through loss-of-function and gain-of-function approaches, we found that CRNDE knockdown markedly reduced cervical cancer cell proliferation, while CRNDE overexpression significantly promoted cervical cancer cell growth. Consistently, CRNDE decreasing obviously inhibited tumorigenicity of cervical cancer cells in vivo, whereas CRNDE increasing markedly promoted cervical cancer progression. Mechanistically, we verified that CRNDE bond to p53 upregulated modulator of apoptosis (PUMA), and PUMA was required for CRNDE to enhance cervical cancer cell growth. Our study demonstrated that CRNDE, combined with PUMA, could be utilized as factor for the clinical diagnosis and prognosis of cervical cancer, and might be potential target for developing effective therapeutic strategy to prevent cervical cancer progression.
宫颈癌是第二常见的妇科恶性肿瘤，仍然是全球女性肿瘤相关死亡的主要原因。长链非编码 RNA（lncRNA）已被证明在肿瘤发生中发挥重要作用，并且几种肿瘤中 lncRNA 结直肠肿瘤差异表达（CRNDE）增加。然而，关于 lncRNA CRNDE 对人宫颈癌的影响知之甚少。本研究旨在探讨 lncRNA CRNDE 表达在人宫颈癌中的临床意义。我们的结果表明，lncRNA CRNDE 在宫颈癌组织和几种宫颈癌细胞系中表达增加。通过功能丧失和功能获得方法，我们发现 CRNDE 敲低显着降低了宫颈癌细胞的增殖，而 CRNDE 过表达显着促进了宫颈癌细胞的生长。一致地，CRNDE 减少明显抑制了体内宫颈癌细胞的致瘤性，而 CRNDE 增加显着促进了宫颈癌的进展。机制上，我们验证了 CRNDE 与 p53 上调凋亡调节剂（PUMA）结合，并且 PUMA 是 CRNDE 增强宫颈癌细胞生长所必需的。我们的研究表明，CRNDE 与 PUMA 结合可作为宫颈癌临床诊断和预后的指标，并可能成为开发有效治疗策略以预防宫颈癌进展的潜在靶标。
