The Role And Clinical Significance Of LINC00978 In Gastric Cancer

Objective:Long noncoding RNAs(LncRNAs)play important roles in the carcinogenesis and development of gastric cancer.The deregulated expression of LINC00978 was reported in human cancers.However,the expression and biological roles of LINC00978 in gastric cancer remain unknown.This study was designed to detect the expression of LINC00978 in gastric cancer cells,gastric cancer tissues and serum samples,and to analyse the correlation between its expression level and clinicopathological factors.Moreover,we studied the functions of LINC00978 in vitro and vivo gastric cancer cells,and investigated the possible mechanism.Materials and methods:(1)QRT-PCR was performed to investigate the expression of LINC00978 in gastric cancer cell lines,tissues and serum samples.The correlation between the expression levels of LINC00978 and the clinicopathological factors(age/ sex/ tumor size/differentiation/ lymph node metastasis/ invasion and TNM stage)was also analyzed.(2)Gastric cancer cells MGC-803 and SGC-7901 were transfected with the shRNA targeting LINC00978.The alterations of gastric cancer cell proliferation,migration,and invasion abilities in vitro were observed.The subcutaneous tumor bearing mouse model was established to observe the changes in tumorigenicity between gastric cancer cell lines after LINC00978 knockdown.Furthermore,we analysed the changes in cell cycle distribution and apoptosis in gastric cancer cells after LINC00978 knockdown.QRT-PCR and western blot were used to detect the changes in cell proliferation and apoptosis related genes and proteins in gastric cancer cells after LINC00978 knockdown.(3)The migration and invasion abilities of gastric cancer cells were observed after LINC00978 kncokdown.QRT-PCR and western blot were used to detect the expression of EMT-related genes after LINC00978 knockdown.The changes in TGF-?/SMAD signaling after LINC00978 knockdown in gastric cancer cells werealso observed.Results:(1)The results of qRT-PCR showed that the expression level of LINC00978 in gastric cancer cells,tissue and serum samples were significantly higher than that in normal control group.Correlation analysis results showed that the expression level of LINC00978 was significantly correlated with tumor size,lymph node metastasis and TNM stage.(2)The expression level of LINC00978 in gastric cancer cells was significantly decreased after LINC00978 knockdown.LINC00978 knockdown inhibited the proliferation of GC cells by suppressing cell cycle progression and inducing apoptosis.The tumorigenic ability of gastric cancer cells in nude mice was significantly decreased after LINC00978 knockdown.(3)The migration and invasion of gastric cancer was decreased after the knockdown of LINC00978.The results of qRT-PCR and western blot showed that LINC00978 knockdown inhibited the activation of TGF-?/SMAD signaling pathway and the process of epithelial-mesenchymal transition(EMT)in gastric cancer cells.Conclusions:The expression of LINC00978 is increased in gastric cancer cells,tissue and serum samples.LINC00978 plays a promoting role in the growth and metastasis of gastric cancer.LINC00978 may serve as a new molecular marker for the diagnosis and treatment of gastric cancer.