Abstract
The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pull-down assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial–mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.
Highlights
Breast cancer is the most common and aggressive malignancy occurring in women worldwide
For the overall survival and prognosis value of tumor suppressor candidate 8 (TUSC8) in breast cancer patients, the curve demonstrated that the high expression of TUSC8 showed better overall survival of breast cancer patients compared with low expression group in TCGA database and GSE dataset (Figure 1C)
For the expression levels of TUSC8 in different stages of breast cancer patients in TCGA cohort, the results suggested that TUSC8 expression reduced gradually from stage I to stage IV (p < 0.05, p < 0.01 respectively) (Figure 1D), indicating that TUSC8 was associated with breast cancer progression
Summary
Breast cancer is the most common and aggressive malignancy occurring in women worldwide. The lncRNA tumor suppressor candidate 8 (TUSC8), named as XLOC_010588 and LINC01071, is located on chromosome 13q14.11 and is a non-protein coding transcript. Previous studies have shown that overexpression of TUSC8 could inhibit the invasion and migration of cervical cancer cells by up-regulating PTEN via miR-641 [12]. Low expression of long non-coding XLOC_010588 indicated a poor prognosis and it played a pivotal role in cervical cancer cell proliferation via decreasing c-Myc expression [13]. Down-regulation of XLOC_010588 inhibited the invasion and migration of colorectal cancer cells through regulating genes associated with EMT [14]. TUSC8 (LINC01071) showed consistent down-regulation in gastric cancer (GC) compared with adjacent non-tumor tissues and was significantly correlated with the age and gender of the GC patients, respectively [15, 16]. Apart from the above studies, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear
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