LARP7 is a potential tumor suppressor gene in gastric cancer

We previously reported frequent truncating mutations of the RNA-binding protein gene, La ribonucleoprotein domain family, member-7 (LARP7) in gastric cancers (GCs) with frequent microsatellite instability. LARP7 negatively regulates positive transcription elongation factor-b (p-TEFb) by binding to and stabilizing 7sk RNA. p-TEFb has been linked to proliferation and de-differentiation in various tissues. Therefore, we reasoned that loss of LARP7 may contribute to gastric tumorigenesis. In this study, we evaluated LARP7 mRNA expression in 18 GCs, their corresponding non-neoplastic gastric tissues (N-GC), and 18 normal gastric tissues from healthy individuals (N-N). We also assessed the effects of transient small interfering (siRNA)-mediated LARP7 knockdown in immortalized non-neoplastic gastric epithelial cells. LARP7 mRNA was significantly decreased in GCs (median 2.5) relative to N(N)s (median 14.9, P < 0.01) as well as relative to their corresponding N(GC)s (median 8.1, P < 0.01). Transfection of an siRNA directed against LARP7 (anti-LARP7 siRNA) into nonneoplastic gastric epithelial cells decreased 7sk levels by 72% relative to a control siRNA (P < 0.01). Furthermore, anti-LARP7 siRNA transfection increased cell proliferation by 23% (P < 0.01) and cell migration by 22% (P < 0.001) relative to control siRNA transfection. Taken together, these findings suggest that LARP7 downregulation occurs early during gastric tumorigenesis and may promote gastric tumorigenesis via p-TEFb dysregulation. Laboratory Investigation (2012) 92, 1013-1019; doi:10.1038/labinvest.2012.59; published online 9 April 2012