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  2. Bioinformatics identification of miR-514b-5p promotes NSCLC progression and induces PI3K/AKT and p38 pathways by targeting small glutamine-rich tetratricopeptide repeat-containing protein beta

Bioinformatics identification of miR-514b-5p promotes NSCLC progression and induces PI3K/AKT and p38 pathways by targeting small glutamine-rich tetratricopeptide repeat-containing protein beta

  • FEBS J. 2022 Sep 30. doi: 10.1111/febs.16639.
Lin Shi  # 1 Jun Kan  # 2 Lin Zhuo 1 Siyun Wang 1 Shaobing Chen 1 Bei Zhang 2 Bin Ke 2
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, 510280, Guangdong, China.
  • 2 Department of VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
  • # Contributed equally.
Abstract

Lung Cancer is the most aggressive Cancer with the highest mortality and incidence rates worldwide. MicroRNAs have been identified as potential targets for non-small cell lung Cancer (NSCLC) treatment. However, the modulatory role of miR-514b-5p in NSCLC progression is little known. Herein, miRNA expression datasets for NSCLC were downloaded from the Cancer Genome Atlas and Gene Ontology Omnibus databases. Gene expression was assessed using qRT-PCR, and western blot analysis, and immunohistochemical (IHC) staining was used to determine protein expression. Gain and loss of function experiments were performed to investigate the impact of miR-514b-5p and small glutamine-rich tetratricopeptide repeat-containing protein beta (SGTB) on cell proliferation and Apoptosis. RNA immunoprecipitation (RIP) and dual-luciferase assays were performed to analyze the target gene of miR-514b-5p. The biological roles of miR-514b-5p were lastly evaluated using nude mouse tumorigenicity assays in vivo. We found that miR-514b-5p was dramatically increased in NSCLC tissues and higher miR-514b-5p expression was associated with poorer overall survival in NSCLC patients. Furthermore, overexpression of miR-514b-5p promoted NSCLC cell growth and suppressed Apoptosis by inducing the activation of the PI3K/Akt and p38 signaling pathways. Mechanistically, dual-luciferase and RIP results highlighted that SGTB was a target gene of miR-514b-5p. Moreover, overexpression of SGTB reduced cell division and promoted Apoptosis in vitro through blocking the PI3K/Akt and p38 signaling pathways. Our findings indicated that miR-514b-5p contributes to carcinoma progression in NSCLC via the PI3K/Akt and p38 signaling pathways by targeting SGTB and this could be a promising diagnostic and therapeutic target for the treatment of NSCLC.

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