Background
Breast cancer (BC) is a common invasive malignancy in women with unclear etiology. A recent study suggested that long non-coding RNA (lncRNA), LINC00968 had a tumor-promoting effect in cancer. However, the role of LINC00968 in BC remains unclear. Therefore, we conducted the present study to determine the effect of LINC00968 in BC and its underlying mechanism.
Conclusion
Taken together, this study suggests that LINC00968 inhibits the progression of BC through impeding hsa-miR-423-5p-mediated PROX1 inhibition. LINC00968 may be a potential therapeutic target for BC therapy that warrants further studies.
Methods
The expression of LINC00968 and hsa-miR-423-5p in BC tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. Dual luciferase reporter, RNA pull-down and RNA immunoprecipitation assays were used to determine the relationship among LINC00968, PROX1 and hsa-miR-423-5p. Gain- and loss-function approaches were utilized to examine the effects of LINC00968, PROX1 and hsa-miR-423-5p on cell proliferation, migration, tube formation in vitro; and tumor growth and angiogenesis in vivo.
Results
LINC00968 expression reduced while hsa-miR-423-5p increased in BC tissues relative to adjacent normal tissues. Overexpression of LINC00968 was observed to inhibit BC cell proliferation, migration and tube formation abilities in vitro as well as tumor growth in vivo through inhibition of hsa-miR-423-5p. And hsa-miR-423-5p mediated BC cellular functions and tumor growth through down-regulating PROX1. LINC00968 was identified as a competing endogenous RNA to upregulate PROX1 by downregulating hsa-miR-423-5p. More importantly, it was found that LINC00968 increased PROX1 expression in vivo in a concentration-dependent manner.