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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.

SUBMITTER: Dai L

PROVIDER: S-EPMC6933345 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Dai Lan L Niu Jixiang J Feng Yanli Y

Journal of cellular and molecular medicine 20191030 1

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 patte ...[more]

PMID: 31668012

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Project description:Objectives Recently long non-coding RNAs (lncRNAs) have emerged as novel gene regulators involved in tumorigenic processes, including oral squamous cell carcinoma (OSCC). Here, we identified a differentiation-related lncRNA, terminal differentiation-induced non-coding RNA (TINCR). However, its biological function and clinicopathological significance in OSCC still remain unclear. Methods The lncRNA expression profiles in OSCC tissues and paired adjacent non-tumor tissues (NATs) from 10 patients were detected by lncRNA microarrays. Weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment were performed to identify the most significant module and module functional annotation, respectively. Potential differentiation-related lncRNAs were screened by differential expression analysis. TINCR was further confirmed in OSCC cell lines and tissues of another patient cohort by using qRT-PCR. The correlation between the TINCR expression level and clinicopathological characteristics was analyzed. The effects of TINCR on cell differentiation, migration and invasion were assessed by knockdown or knock-in in vitro and in vivo. Results WGCNA and GO enrichment analysis showed that one co-expression network was significantly enriched for epithelial cell differentiation, among which, TINCR was significantly downregulated. qRT-PCR analyses validated down-regulation of TINCR in tumor tissues compared with paired NATs, and its expression was closely correlated with pathological differentiation and lymph node metastasis in patients with OSCC. Patients with lower TINCR expression levels had worse survival. Cell function experiments showed that TINCR played a crucial role in epithelial differentiation. Both TINCR and epithelial differentiation-associated genes, including IVL and KRT4, were significantly upregulated during OSCC cell calcium-induced differentiation but were reduced when cell dedifferentiation occurred in tumor spheres. Overexpression of TINCR dramatically suppressed cell dedifferentiation, migration and invasion in vitro, while knockdown of TINCR had the opposite effects. Upregulation of TINCR significantly elevated the expression of terminal differentiation genes and repressed tumor growth in vivo. Moreover, TINCR significantly suppressed the activation of JAK2/STAT3 signaling in OSCC cells. Conclusion Our study suggests that TINCR functions as a tumor suppressor by inducing cell differentiation through modulating JAK2/STAT3 signaling in OSCC. TINCR may serve as a prognostic biomarker and therapeutic target for OSCC.

Project description:BackgroundRetinoic acid induced 14 (RAI14), also known as NORPEG, is reported as being deregulated in non-small-cell lung cancer, together with having involvement in its cell proliferation as a super enhancer related gene.PurposeThe objective of this study was to investigate the role of RAI14 in the progression and metastasis of gastric cancer and explore the associated mechanism.Materials and methodsGEPIA database was used to analyze the expression of RAI14 in gastric cancer. MNK45 and AGS cells were transfected with siRNA-RAI14 to block the expression of RAI14. Cell Counting Kit 8 and colony formation assays were performed to measure cell proliferation. Cell migration and invasion capacities was examined by transwell assay. Apoptosis rate was detected using flow cytometry, and the protein levels of apoptosis-related proteins was determined using Western blot assay. Reverse-transcription PCR assay was used to detect the expressions of RAB31.ResultsGene expression profiling interactive analysis revealed that RAI14 was substantially upregu-lated in gastric cancer and higher expression of RAI14 was associated with worse prognosis. We also observed that the knockdown of RAI14 by siRNA-RAI14 transfection suppressed growth capacity of MKN45 and AGS cells. Also, RAI14 knockdown inhibited migration and invasion of MKN45 and AGS cells in vitro. Moreover, RAI14 knockdown was observed to accelerate cell apoptosis via down-regulation of Bcl-2 and upregulation of Bax in MKN45 and AGS cells. Furthermore, downregulation of RAI14 inhibited the activation of Akt pathway, and activation of Akt by IGF-1 could restore the reduced proliferation induced by RAI14 knockdown. In addition, we found that RAI14 had a positive correlation with the RAB31 in gastric cancer by GEPIA reverse-transcription PCR and Western blot assays, and the reduced proliferation caused by RAI14 knockdown was restored by RAB31.ConclusionRAI14 knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31 might be a downstream target gene of RAI14, providing a novel sight into the molecular mechanism of RAI14 and a potential target for gastric cancer treatment.

Dataset Information

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

Publications

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

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