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J Exp Clin Cancer Res. 2018 Nov 27;37(1):289. doi: 10.1186/s13046-018-0945-6.

Long noncoding RNA LINC00511 contributes to breast cancer tumourigenesis and stemness by inducing the miR-185-3p/E2F1/Nanog axis.

Author information

1
Department of Mammary and Thyroid Gland Surgery, Youjiang Medical College Affiliated Hospital, Baise, 533000, Guangxi, China.
2
The First Affiliated Hospital of Jinan university, Huangpu Road, No. 613, Guangzhou, 510630, Guangdong, China.
3
Department of Oncology, Youjiang Medical College Affiliated Hospital, Baise, 533000, Guangxi, China.
4
Department of Dental, Youjiang Medical College Affiliated Hospital, Baise, 533000, Guangxi, China.
5
The First Affiliated Hospital of Jinan university, Huangpu Road, No. 613, Guangzhou, 510630, Guangdong, China. huangshiq97@126.com.
6
Department of Oncology, Youjiang Medical College Affiliated Hospital, Baise, 533000, Guangxi, China. huangshiq97@126.com.
7
Department of Tumor, Youjiang Medical College Affiliated Hospital, Zhongshan Second Road, No. 18, Baise, 533000, Guangxi, China. huangshiq97@126.com.
8
Department of Oncology, Youjiang Medical College Affiliated Hospital, Baise, 533000, Guangxi, China. weizhongh_yjmc@aliyun.com.

Abstract

BACKGROUND:

Emerging evidence have illustrated the vital role of long noncoding RNAs (lncRNAs) long intergenic non-protein coding RNA 00511 (LINC00511) on the human cancer progression and tumorigenesis. However, the role of LINC00511 in breast cancer tumourigenesis is still unknown. This research puts emphasis on the function of LINC00511 on the breast cancer tumourigenesis and stemness, and investigates the in-depth mechanism.

METHODS:

The lncRNA and RNA expression were measured using RT-PCR. Protein levels were measured using western blotting analysis. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Sphere-formation assay was also performed for the stemness. Bioinformatic analysis, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried to confirm the molecular binding.

RESULTS:

LINC00511 was measured to be highly expressed in the breast cancer specimens and the high-expression was correlated with the poor prognosis. Functionally, the gain and loss-of-functional experiments revealed that LINC00511 promoted the proliferation, sphere-formation ability, stem factors (Oct4, Nanog, SOX2) expression and tumor growth in breast cancer cells. Mechanically, LINC00511 functioned as competing endogenous RNA (ceRNA) for miR-185-3p to positively recover E2F1 protein. Furthermore, transcription factor E2F1 bind with the promoter region of Nanog gene to promote it transcription.

CONCLUSION:

In conclusion, our data concludes that LINC00511/miR-185-3p/E2F1/Nanog axis facilitates the breast cancer stemness and tumorigenesis, providing a vital insight for them.

KEYWORDS:

Breast cancer stem cells; E2F1; LINC00511; Nanog; miR-185-3p

PMID:
30482236
DOI:
10.1186/s13046-018-0945-6
Free PMC Article

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