Kallikrein 12 downregulation reduces AGS gastric cancer cell proliferation and migration

Abstract

ABSTRACT. Abnormal expression of the kallikrein (KLK) family of serine proteases closely correlates with onset, progression, and prognosis of endocrine gland-related malignant tumors. The aim of this study was to evaluate how downregulation of KLK12 influenced cell cycle and proliferation of the AGS gastric cancer cell line. KLK12 was detected by western blot in GES-1 normal gastric epithelial and AGS cells. AGS cells were transfected with KLK12 siRNA, a negative control siRNA, or subjected to a mock transfection, following which, we assessed mRNA and protein levels, cell proliferation, cell migration, and cell cycle progression. We found that KLK12 levels were significantly higher in AGS cells than in GES-1 cells. Transfection of AGS cells with KLK12 siRNA led to downregulation of KLK12 mRNA and protein expression, reduced cell proliferation (0.47 ± 0.03 vs 0.92 ± 0.04, P < 0.01), and lower cell counts (3.92 ± 0.25 x 10 5 vs 5.47 ± 0.50 x 10 5 , P < 0.01) with respect to the negative control. We observed that KLK12 siRNA increased the number of AGS cells in G0/G1 and reduced those in S phase. Furthermore, downregulation of KLK12 in AGS cells decreased their ability to penetrate the membrane in a migration assay (P < 0.05).In conclusion, KLK12 siRNA inhibited the proliferation and migration of AGS gastric cancer cells and caused their arrest in the G0/G1 phase of the cell cycle.

CASC15 contributes to proliferation and invasion through regulating miR-766-5p/ KLK12 axis in lung cancer

“…Cells transfected with both CASC15 and miR-766-5p inhibitor exhibited proliferation, colony formation, migration and invasion similar to those of the cells transfected with si-NC. Further, we show that the cancer proliferation and invasion marker, kallikrein-related peptidase 12 (KLK12) [20][21][22], was inhibited by si-CASC15 but promoted by miR-766-5p inhibitor, while transfection of both did not alter KLK12 expression significantly (Figure 4(e)). These evidences corroborated the antagonizing effects of miR-766-5p inhibitor and si-CASC15.…”

Prognostic value of kallikrein-related peptidase 12 (KLK12) mRNA expression in triple-negative breast cancer patients

“…These observations are consistent with the currently known functions of the KLK12 protease; indeed, the functional studies performed to date argue for a pro-tumorigenic role of this protease. Blocking KLK12 expression in gastric cancer cells significantly inhibited proliferation by arresting cells in G0/G1 phase (Li and He 2016;Zhao et al 2012). KLK12 also regulates cell adhesion and migration of endothelial and malignant cells likely through the cleavage of structural components of the extracellular matrix (ECM) (Li and He 2016;Zhao et al 2012;Kryza et al 2018).…”

“…Blocking KLK12 expression in gastric cancer cells significantly inhibited proliferation by arresting cells in G0/G1 phase (Li and He 2016;Zhao et al 2012). KLK12 also regulates cell adhesion and migration of endothelial and malignant cells likely through the cleavage of structural components of the extracellular matrix (ECM) (Li and He 2016;Zhao et al 2012;Kryza et al 2018). Furthermore, KLK12 has been reported for its proangiogenic effect, thereby displaying a crucial role in the process of cancer.…”

“…KLK12 induced cell growth of microvascular endothelial cells (MVEC) in skin (Giusti et al 2005) as well as MVEC migration and capillary morphogenesis in skin and lung (Giusti et al 2005;Guillon-Munos et al 2011;Kryza et al 2013Kryza et al , 2014Kryza et al , 2018. Beside its implications in angiogenesis, KLK12 may also play a role in proliferation and migration of cancer cells, as described for gastric cancer cells in vitro (Li and He 2016;Zhao et al 2012). As the tumor microenvironment may modulate the biological consequences of KLK actions, it may be desirable to study the KLK12 expression in a homogeneous cohort comprising only one cancer subtype.…”

“…The KLK12 gene belongs to the kallikrein gene cluster (Yousef et al 2000) and is expressed in a variety of normal tissue including colon, salivary glands, stomach, trachea and vagina (Shaw and Diamandis 2007). Deregulation of KLK12 expression has been observed in gastric (Li et al 2017) and skin (Giusti et al 2005(Giusti et al , 2006 disorders, and in gastric (Li and He 2016;Zhao et al 2012), salivary gland (Morrison et al 2018), prostate (Memari et al 2007), breast (Papachristopoulou et al 2018;Talieri et al 2012) and lung tumors (Planque et al 2008;Swarts et al 2013;Guillon-Munos et al 2011). The currently known functions of the KLK12 protease are mainly related to angiogenesis.…”