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CREB1 acts via the miR‑922/ARID2 axis to enhance malignant behavior of liver cancer cells.

ABSTRACT: There is little information on the role of microRNA (miR)‑922 in the malignant behavior of liver cancer. The present study investigated the regulation of miR‑922 expression levels by cAMP response element binding protein 1 (CREB1) in liver cancer tissue, its role in regulating malignant behavior and its potential targets in liver cancer. miR‑922 expression in liver cancer cells and tissue was determined by reverse transcription‑quantitative PCR. The binding of CREB1 to the promoter region of mir‑922 was tested by chromatin immunoprecipitation‑PCR. The predicted AT‑rich interactive domain 2 (ARID2) and fidgetin, microtubule severing factor targets of miR‑922 were characterized by dual luciferase reporter assay. The effects of altered ARID2 expression levels on miR‑922‑enhanced malignant behavior of liver cancer cells were tested. CREB1 bound to the promoter region of miR‑922. Elevated miR‑922 transcripts were inversely associated with ARID2 expression in liver cancer tissue and cells. miR‑922 inhibited ARID2‑regulated luciferase expression and was present in the miR/argonaute RISC catalytic component 2 complex. ARID2 significantly decreased malignant behavior of liver cancer MHCC97L cells. Similarly, ARID2 over‑expression inhibited growth of xenograft liver cancer tumors and decreased miR‑922, Bcl‑2, proliferating cell nuclear antigen, cyclin D1, MMP3 and MMP9 expression and serum VEGF and TNF‑α levels, but enhanced Bax expression levels in tumors. ARID2 over‑expression abrogated malignant behavior promoted by miR‑922 over‑expression and enhanced miR‑922‑decreased malignant behavior of liver cancer cells. CREB induced miR‑922 transcription, which targeted ARID2 to enhance malignant behavior of liver cancer cells, indicating that the CREB1/miR‑922/ARID2 axis may be a potential target for liver cancer treatment.

SUBMITTER: Liu X

PROVIDER: S-EPMC8020205 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBreast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear.MethodsWe conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis.ResultsTDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC.ConclusionsOur study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

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CREB1 acts via the miR‑922/ARID2 axis to enhance malignant behavior of liver cancer cells.

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