LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK ssignalling pathway.

Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared to the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with ER-negative, PR-negative, advanced TMN stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 MAPK gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

[1]  P. Chueh,et al.  MicroRNA-708 activation by glucocorticoid receptor agonists regulate breast cancer tumorigenesis and metastasis via downregulation of NF-&kgr;B signaling , 2019, Carcinogenesis.

[2]  Lihua Li,et al.  hsa_circRNA_0006528 as a competing endogenous RNA promotes human breast cancer progression by sponging miR‐7‐5p and activating the MAPK/ERK signaling pathway , 2018, Molecular carcinogenesis.

[3]  Lihua Li,et al.  Med19 is targeted by miR-101-3p/miR-422a and promotes breast cancer progression by regulating the EGFR/MEK/ERK signaling pathway. , 2019, Cancer letters.

[4]  Lihua Li,et al.  Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer , 2018, Journal of cellular biochemistry.

[5]  Wanyeon Kim,et al.  Roles of Oncogenic Long Non-coding RNAs in Cancer Development , 2018, Genomics & informatics.

[6]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[7]  S. Kim,et al.  A Kelch domain-containing KLHDC7B and a long non-coding RNA ST8SIA6-AS1 act oppositely on breast cancer cell proliferation via the interferon signaling pathway , 2018, Scientific Reports.

[8]  W. Biernat,et al.  Estrogen receptor-negative progesterone receptor-positive breast cancer - "Nobody's land" or just an artifact? , 2018, Cancer treatment reviews.

[9]  Li Lin,et al.  The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1 , 2018, Molecular Cancer.

[10]  C. Peng,et al.  Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer , 2017, Molecular Cancer.

[11]  Qiang Sun,et al.  Long non-coding RNA PTENP1 inhibits proliferation and migration of breast cancer cells via AKT and MAPK signaling pathways , 2017, Oncology letters.

[12]  W. Liu,et al.  IL-33 restricts invasion and adhesion of trophoblast cell line JEG3 by downregulation of integrin α4β1 and CD62L , 2017, Molecular medicine reports.

[13]  Yanyan Ping,et al.  Oncogenic long noncoding RNA landscape in breast cancer , 2017, Molecular Cancer.

[14]  Zheng Wang,et al.  A long non-coding RNA signature to improve prognosis prediction of gastric cancer , 2016, Molecular Cancer.

[15]  Fan Yang,et al.  Oncotargets and Therapy Dovepress Expression Profile Analysis of Long Noncoding Rna in Her-2-enriched Subtype Breast Cancer by Next- Generation Sequencing and Bioinformatics , 2022 .

[16]  Yu Sun,et al.  Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis , 2015, Journal of receptor and signal transduction research.

[17]  Juan Li,et al.  The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression , 2015, Molecular Cancer.

[18]  S. Koul,et al.  Role of p38 MAP Kinase Signal Transduction in Solid Tumors. , 2013, Genes & cancer.