Abstract
BackgroundRecent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcinogenesis. However, its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Furthermore, we also identified the potential miRNA directly targeting LAMA4.MethodsWestern blot, Real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) were used to detect the expression of LAMA4 in TNBC. The effects of LAMA4 on TNBC cell proliferation, migration and invasion were also explored in vitro. The potential miRNA that targets LAMA4 was determined by dual luciferase reporter assay and verified by qPCR and western blot analysis.ResultsOur study showed LAMA4 mRNA (p = 0.001) and protein (p = 0.005) expression in TNBC tissue samples were elevated compared with adjacent normal tissue samples, and LAMA4 was mainly expressed in the cytoplasm of breast carcinoma cells. Knockdown of LAMA4 inhibited TNBC cell proliferation, migration and invasion in vitro. Moreover, further study revealed that LAMA4 was a putative target of miR-539, and miR-539 negatively regulated LAMA4 expression by directly targeting its 3′-UTR.ConclusionsOur study suggested that miR-539 suppressed the expression of LAMA4. LAMA4 plays an important role in tumor progression and may be an important target in treatment of TNBC.
Highlights
Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcino‐ genesis
Expression of LAMA4 is increased at both mRNA and protein level in triple-negative breast cancer (TNBC) tissues To determine whether LAMA4 plays a pivotal role in TNBC, western blotting assays and quantitative PCR were performed in TNBC and adjacent normal tissues
There were negative expression of LAMA4 (Fig. 1f ). These data suggest that LAMA4 was mostly overexpressed in TNBC tissues compared with adjacent normal tissues
Summary
Recent studies have shown that laminin subunit alpha 4 (LAMA4) plays an important role in carcino‐ genesis. Its molecular biological function in triple-negative breast cancer (TNBC) has not been entirely clarified. This study investigated the expression of LAMA4 in TNBC and its effect on cell proliferation, migration and invasion. Triple-negative breast cancer (TNBC) is the most invasive and aggressive one among the breast cancer subtypes [3], lacking expression of α-estrogen, progesterone and HER2(erbB2)receptors and characterized by high mitotic rate, increased lymphocytic infiltrate,high grade and large tumor size [4, 5]. It has been reported that LAMA4 plays a role in formation and function of endothelium, transmigration of inflammatory cells through endothelium and invasion of certain tumors [11,12,13]. We are curious about its role in TNBC and think it may be important for TNBC progress
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