Long non‑coding RNA SNHG7 inhibits NLRP3‑dependent pyroptosis by targeting the miR‑34a/SIRT1 axis in liver cancer

Abstract

Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) is involved in a variety of different types of cancer; however, the role of SNHG7 during liver cancer progression is not completely understood. The aim of the present study was to investigate the functional role and regulatory mechanism underlying SNHG7 during liver cancer. A total of 25 paired hepatocellular carcinoma (HCC) tumor tissues and adjacent normal tissues were collected. Reverse transcription-quantitative PCR and western blotting were performed to detect the expression levels of SNHG7, microRNA (miR)-34a, sirtuin 1 (SIRT1) and pyroptosis-related targets. RNA fluorescence in situ hybridization was performed to detect the expression of SNHG7 in HCC tissues. SNHG7 expression was upregulated in HCC tissues and liver cancer cells compared with normal tissues and normal liver cell lines. High expression of SNHG7 inhibited NLR family pyrin domain containing 3 (NLRP3)-dependent pyroptosis in HepG2 and SK-hep-1 cells. Bioinformatics analysis and dual-luciferase reporter assays were performed to investigate the interactions between miR-34a and SNHG7 or SIRT1. SNHG7 served as a competing endogenous RNA of miR-34a, and SIRT1 was identified as a direct target of miR-34a. Cell pyroptosis was evaluated by TUNEL and lactate dehydrogenase release assays. SNHG7 knockdown reduced SIRT1 expression, but increased the expression levels of NLRP3, caspase-1 and interleukin-1β, leading to pyroptosis. SNHG7 knockdown-induced effects were enhanced by miR-34a upregulation. In summary, the present study indicated that the SNHG7/miR-34a/SIRT1 axis contributed to NLRP3-dependent pyroptosis during liver cancer.

Golgi phosphoprotein 3 promotes the proliferation of gallbladder carcinoma cells via regulation of the NLRP3 inflammasome

“…Several studies have reported that the activation of the NLRP3/Caspase-1 pathway is associated with tumor progression (24)(25)(26)(27). Wang et al (25) found that when the NLRP3 inflammasome is activated, Caspase-1 is spliced to further activate the Akt, GSK-3p, ERK1/2 and CREB signaling pathways to promote tumor proliferation.…”

“…Physiological levels of NLRP3 activation protects the body's inflammatory immune system via activation of Caspase-1, whereas uncontrolled activation will lead to dysregulated inflammation, autoimmune diseases, neurodegenerative diseases, and even malignant tumors (20)(21)(22)(23)(24). Recently, a number of studies have reported that the overactivation of NLRP3 is closely associated with the progression of several malignant tumors (24)(25)(26)(27). To date, there are numerous studies on the downstream effects of NLRP3 (22)(23)(24)(25).…”

Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis

“…In liver cancers, SNHG7 worked as a ceRNA of miR-34a, and SIRT1 was proved to be a direct target of miR-34a. Interference with SNHG7 down-regulated the expression of SIRT1, but up-regulated the levels of NLRP3, caspase-1, and interleukin-1beta, which induced pyroptosis, suggesting NLRP3-dependent pyroptosis was induced through SNHG7/miR-34a/SIRT1 signaling pathway during liver cancer [ 64 ]. Kcnq1ot1 regulated the level of caspase-1 by working as a sponge of miR-214-3p.…”

The Crosstalk Between Long Non-Coding RNAs and Various Types of Death in Cancer Cells

“… 90 , 91 Pyroptosis is connected to the clearing of various bacterial and viral infections by eliminating intracellular replication niches and increasing the host’s defensive responses. 92 The correct pyrolysis pathway may increase pathogen clearance efficiency and promote adaptive immune stimulation. Researchers believe that inducing tumor pyroptosis may be a potential treatment strategy.…”