Knockdown of long non‐coding RNA LINC00176 suppresses ovarian cancer progression by BCL3‐mediated down‐regulation of ceruloplasmin

Abstract

Ovarian cancer is a common malignancy among women with some clinically approved diagnostic coding gene biomarkers. However, long non‐coding RNAs (lncRNAs) have been indicated to play an important role in controlling tumorigenesis of ovarian cancer. Hereby, the aim of the study was to uncover the function of lncRNA LINC00176 in the development and progression of ovarian cancer by regulating ceruloplasmin (CP). Bioinformatics prediction in combination with RT‐qPCR analysis for the expression pattern of LINC00176 revealed that LINC00176 was highly expressed in ovarian cancer tissues as well as in ovarian cancer cell lines, respectively. LINC00176 was predominantly localized in the nucleus. Delivery of si‐LINC00176, oe‐LINC00176, si‐BCL3 and si‐CP plasmids was conducted to explore the effects of LINC00176 on ovarian cancer. Promoted proliferation, migration and invasion along with reduced apoptosis were observed in cells treated with oe‐LINC00176, while si‐BCL3 and si‐CP were able to block the promoting effects. Investigations with regard to the correlation between LINC00176 and promoter region of CP turned out to be positive via B‐cell CLL/lymphoma 3 (BCL3) by means of dual‐luciferase reporter gene assay, ChIP and RIP assays. Furthermore, oncogenic properties of the LINC00176/BCL3/CP axis were also demonstrated by tumour formation in vivo generated upon injecting cells in nude mice. Our results demonstrate that restored LINC00176 initiates tumorigenesis in ovarian cancer by increasing CP expression via recruiting BCL3, the mechanism of which represented a potential and promising therapeutic target for the disease.

The Challenges and Opportunities of LncRNAs in Ovarian Cancer Research and Clinical Use

“…These categories are not mutually exclusive. For instance, Linc00176 acts as a scaffold to keep BCL3 and p50 together (NF-κB family) and at the same time recruits this complex to the ceruloplasmin promoter to activate its expression [139]. Some reports of transcriptional regulation by lncRNAs do not fit this classification at all, as in the case of FAL1, which increases the stability of BMI (another subunit of PRC), thereby allowing epigenetic marking of the p21 gene to be silenced [31,42].…”

Long non-coding RNA FAM83H-AS1 acts as a potential oncogenic driver in human ovarian cancer

“…For example, lncRNA LINC00176 was highly expressed in OC tissues as well as in OC cell lines, respectively. Knockdown of lncRNA LINC00176 suppresses OC progression by BCL-mediated downregulation of ceruloplasmin [12]. Li et al suggested that lncRNA UCA1 was upregulated in cisplatin-resistant patient tissues and cell lines.…”

Long non-coding RNA FAM83H-AS1 acts as an oncogenic driver in human ovarian cancer

“…For example, lncRNA LINC00176 was highly expressed in OC tissues as well as in OC cell lines, respectively. Knockdown of lncRNA LINC00176 suppresses OC progression by BCL-mediated downregulation of ceruloplasmin [12]. Li et al suggested that lncRNA UCA1 was upregulated in cisplatinresistant patient tissues and cell lines.…”