Abstract
Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play a significant role in regulating gene expression and participating in the progression of various malignancies. In our study, by analyzing data from The Cancer Genome Atlas (TCGA), LINC00536 was found to be highly expressed in breast cancer (BC) tissues, but its function and clinical significance in BC are still unknown. Therefore, we aimed to explore the role and molecular mechanism of LINC00536 in BC. We collected human BC tissue specimens and validated that LINC00536 was overexpressed in BC tissues. Increased LINC00536 expression was associated with advanced TNM stage, larger tumor diameter, lymph node metastasis and poor prognosis in patients with BC. Univariate and multivariate Cox regression analyses showed that high LINC00536 expression was an independent prognostic risk factor for overall survival in BC patients. Furthermore, quantitative reverse transcription PCR (qRT-PCR) showed that LINC00536 was upregulated in BC cell lines. Then, we confirmed that LINC00536 silencing-inhibited BC cell proliferation, migration, and invasion and led to cell cycle arrest in vitro. Animal experiments showed that knockdown of LINC00536 expression suppressed tumorigenesis in vivo. Mechanistically, LINC00536 serves as a ceRNA for miR-214-5p, increasing the expression of ROCK1, which acts as a tumor promoter in BC. Rescue assays revealed that miR-214-5p inhibition or ROCK1 overexpression could neutralize the suppressive effects of LINC00536 knockdown on cell proliferation, migration and invasion. Our data indicated that LINC00536 accelerates BC progression by regulating the miR-214-5p/ROCK1 pathway, which might provide a new perspective to investigate the development process of BC.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- BC:
-
Breast cancer
- TCGA:
-
The Cancer Genome Atlas
- IARC:
-
International Agency for Research on Cancer
- qRT-PCR:
-
Quantitative reverse transcription PCR
- lncRNA:
-
Long noncoding RNA
- ncRNAs:
-
Noncoding RNAs
- miRNA:
-
MicroRNA
- mRNA:
-
Messenger RNA
- FDR:
-
False discovery rate
- EMT:
-
Epithelial-mesenchymal transition
- shRNA:
-
Short hairpin RNA
- ceRNA:
-
Competitive endogenous RNA
- cDNA:
-
Complementary DNA
- ROCK1:
-
Recombinant Rho Associated coiled coil containing Protein Kinase 1
- WB:
-
Western blot
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Funding
This work was financially supported by grants from the National Natural Science Foundation of China (81902932), Wuxi Taihu Lake Talent Plan, Supports for Leading Talents in Medical and Health Profession (to Lihua Li), and Wuxi Municipal Bureau on Science and Technology (N20192029).
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CH and XZ designed the study, performed the experiments, analyzed the statistical data and wrote the manuscript. KF provided assistance in obtaining clinical follow-up information. LL and ZG supervised the study and revised the paper. All authors approved this manuscript.
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This project was authorized by the Medical Ethics Committee of Jiangnan University Affiliated Hospital. All patients signed informed consent forms, and the study was approved by the Ethical Committee of the Affiliated Hospital of Jiangnan University. All the experiments in this study were conducted in accordance with the principles outlined in the Declaration of Helsinki.
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Hu, C., Zhang, X., Fang, K. et al. LINC00536 Promotes Breast Cancer Progression by Regulating ROCK1 via Sponging of miR-214-5p. Biochem Genet 61, 1163–1184 (2023). https://doi.org/10.1007/s10528-022-10304-6
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DOI: https://doi.org/10.1007/s10528-022-10304-6