Cancer‐testis gene PIWIL1 promotes cell proliferation, migration, and invasion in lung adenocarcinoma

Abstract

Piwi‐like RNA‐mediated gene silencing 1 (PIWIL1) has been identified as a novel extremely highly expressed cancer‐testis (CT) gene in lung adenocarcinoma. However, the exact function and mechanism of PIWIL1 in lung adenocarcinoma remains unclear. Herein, we sought to investigate the role of PIWIL1 in the occurrence and development of lung adenocarcinoma. We examined the expression pattern of PIWIL1 in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples, and validated it by Real‐Time PCR (RT‐PCR) in additional 21 paired lung adenocarcinoma tissues and 16 normal tissues. Subsequently, we explored the biological function of PIWIL1 in A549 and H1299 cell lines by gain and loss‐of‐function analyses. Using TCGA lung adenocarcinoma data, we further performed coexpression and Gene Ontology (GO) analyses, and analyzed the association of DNA methylation levels in PIWIL1 promoter region with its expression. Finally, we evaluated its expression in different mutation status of significantly mutated genes (SMGs) in TCGA lung adenocarcinoma data. We observed that PIWIL1 was expressed in testis and lung adenocarcinoma but not in other normal tissues, and its high expression was associated with shortened survival of lung cancer patients. Overexpression of PIWIL1 could facilitate the proliferation, invasion and migration of lung adenocarcinoma cells and vice versa. GO analysis revealed that PIWIL1 upregulated genes were enriched in embryonic development, cell proliferation and regulation of transcription. Moreover, promoter DNA hypomethylation of PIWIL1 could contribute to its aberrant expression in tumors. Interestingly, PIWIL1 expression was significantly higher in patients without hepatocyte growth factor (HGF) or serine/threonine kinase 11 (STK11) mutation (P = 0.006 and 0.005, respectively). PIWIL1 is an epidriver gene in lung adenocarcinoma, indicating a potential target for further therapy.

The impact of the RASSF1C and PIWIL1 on DNA methylation: the identification of GMIP as a tumor suppressor

“…This, in turn, is a potential mechanism through which RASSF1C-PIWIL1-piRNA pathway may promote lung cancer cell metastasis. It has been reported that PIWIL1 promotes lung cancer cell proliferation, migration, and invasion; and PIWIL1 knockdown in LCSCs resulted in growth inhibition both in vitro and in vivo in a nude mouse model [24][25][26]. We should also note that PIWIL1 expression in lung tumor adenocarcinoma has been reported to be regulated by promoter DNA methylation and PIWIL expression has been correlated with the expression of gene signatures associated with stem cells [12,24].…”

“…It has been reported that PIWIL1 promotes lung cancer cell proliferation, migration, and invasion; and PIWIL1 knockdown in LCSCs resulted in growth inhibition both in vitro and in vivo in a nude mouse model [24][25][26]. We should also note that PIWIL1 expression in lung tumor adenocarcinoma has been reported to be regulated by promoter DNA methylation and PIWIL expression has been correlated with the expression of gene signatures associated with stem cells [12,24]. Elevated PIWIL1 expression in lung tumors is associated with poor patient prognosis and it has been suggested as an independent prognostic marker [12,24].…”

Estrogen-ERα signaling and DNA hypomethylation co-regulate expression of stem cell protein PIWIL1 in ERα-positive endometrial cancer cells

“…Gain of 5′ end promoter CpG island methylation for the PIWIL1 is in association with their transcriptional silencing [23]. Promoter DNA hypomethylation of PIWIL1 could also contribute to its aberrant expression [24,25]. In our previous study, we found that PIWIL1 was silenced in normal endometrium and reactivated in endometrial cancer [9].…”

“…Previous study observed the existence of promoter CpG island hypermethylation-associated silencing of PIWIL1 in primary seminoma and non-seminoma testicular tumors [23]. Some studies also found that promoter DNA hypomethylation of PIWIL1 could contribute to its aberrant expression in lung adenocarcinoma [24,25]. However, the relationship between DNA methylation status of PIWIL1 promoter and PIWIL1 expression in endometrial cancer is unknown.…”

KK-LC-1 May Be An Effective Prognostic Biomarker for Gastric Cancer

“…In lung adenocarcinoma, PIWIL1 is considered to be a highly expressed CT gene. Hypomethylation of the promoter DNA of PIWIL1 can cause overexpression of CT genes [32]. However, So far, there are few reports on the function and mechanism of KK-LC-1 in human malignant tumors.…”