Long intergenic noncoding RNA 00844 promotes apoptosis and represses proliferation of prostate cancer cells through upregulating GSTP1 by recruiting EBF1

Abstract

Accumulating evidence have suggested the function of long noncoding RNAs as crucial players in the pathogenesis of prostate cancer (PC), a urologic tumor in male with poor prognosis. This study was designed to explore the functions of long intergenic noncoding RNA 00844 (LINC00844) in PC progression. The expression of LINC00844 and glutathione S‐transferase P1‐1 (GSTP1) was detected by reverse transcription quantitative polymerase chain reaction, followed by the identification of the relationship among LINC00844, GSTP1, and early B cell factor 1 (EBF1) by dual luciferase reporter gene assay, RNA immunoprecipitation assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay. Using loss‐ and gain‐of‐function assays, the effects of LINC00844, GSTP1, and EBF1 on the biological characteristics of PC cells were assessed by cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine assay, and flow cytometry. Lastly, the results from in vitro experiments were verified in vivo by establishing a xenograft tumor model in nude mice. LINC00844 and GSTP1 both displayed low expression in PC tissues and cells. LINC00844 positively regulated the expression of GSTP1 via recruiting EBF1. Overexpression of LINC00844 reduced proliferation and elevated apoptosis of PC cells through recruiting EBF1, which subsequently upregulated GSTP1. In vivo experiments confirmed that LINC00844 or GSTP1 upregulation attenuated tumor growth. LINC00844 elevated GSTP1 expression by recruiting EBF1 to the promoter region of GSTP1, thereby suppressing PC progression. Hence, LINC00844 is a novel therapeutic target for the development of new treatment protocols for PC.

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

“…[277] Long intergenic noncoding RNA 00844 recruits early B cell factor 1 to the GSTP1 promoter, inducing its expression and leading to the attenuated growth of prostate cancer. [255] GSTM1 overexpression reduces ROS and elevates GSH and TP53. [249] GSTZ1 downregulation reduces GSH, contributing to the promotion of oxidative stress and the constitutive activation of the KEAP1/NRF2 pathway, thus promoting cancer progression.…”

“…In addition, GSTA1, GSTM1, and GSTZ1 are reported to be downregulated in tumor tissue and can correlate with a poor prognosis [63,[248][249][250][251], while GSTT1, GSTO1, and GSTK1 are mostly reported to be upregulated in tumor tissue compared to the normal surrounding tissue [252,253]. The expression level of GSTP1 in tumor tissue is controversial [144,[253][254][255], and its involvement in tumorigenesis could at least in part depend on its hypermethylation [256][257][258][259][260]. Table 4.…”

“…[259] Tumor tissues have low GSTP1 expression. [255] Undetectable methylated GSTP1 DNA in serum correlates with a better prognosis. [260] Thyroid cancer Papillary thyroid carcinoma tissue has a higher expression of GPX7 compared to nodular goiter.…”

“…Additionally, miR-133b downregulates GSTP1 by targeting GSTP1 3 -UTR [276]. GSTP1 is also downregulated by the methylation of the CpG island [277], while the recruitment of early B cell factor 1 to its promoter upregulates GSTP1 [255]. The overexpression of GSTP1 can induce cell cycle arrest [254], as well as GPX4 deficiency [278], and can thus be used as potential targets in anticancer therapy.…”

GSTP1 as a novel target in radiation induced lung injury

“…It is a dimeric protein composed of two same subunits with a molecular weight of 22.5 kDa [20]. Recent research shows that GSTP1 plays a vital role in maintaining the balance of cell oxidation and regulating cell proliferation and apoptosis [21][22][23]. Furthermore, clinical data finds that patients with GSTP1 SNP 105Ile/Val had significantly higher risk of radiation pneumonitis (RP) of grade ≥ 2 (P = 0.001), which strongly indicates that GSTP1 is closely associated with the occurrence and development of RILI [11].…”