Knockdown of Long Non-coding RNA PCAT-1 Inhibits Myeloma Cell Growth and Drug Resistance Via P38 and JNK MAPK Pathways

Overview

Journal J Cancer

Specialty Oncology

Date 2019 Nov 29

PMID 31777580

Citations 20

Authors

Xianjuan Shen

Pei Shen

Qian Yang

Qingqing Yin

Feng Wang

Hui Cong

Xudong Wang

Shaoqing Ju

Affiliations

Soon will be listed here.

Abstract

Both previous and recent literature showed long non-coding RNAs (lncRNAs) were crucial participants in multiple myeloma (MM) evolution. However, the dynamic regulation and mechanism of lncRNAs in MM progression was not fully understood. This study will explore the expression and effects of prostate cancer-associated ncRNA transcript 1 (PCAT-1) in MM. The expression level of PCAT-1 was examined using quantitative real-time PCR in patients with newly diagnosed MM and cell lines. The potential biological effects and molecular mechanisms of PCAT-1 in MM were evaluated using a series of soft agar colony formation assay, CCK-8 assay, cell cycle and apoptosis assay by flow cytometry, protein chip arrays, western blot analysis, immunohistochemistry and nude subcutaneous tumorigenesis model. High expression of PCAT-1 was observed in patients with newly diagnosed MM and cell lines. Over-expressed PCAT-1 enhanced cell division and inhibited apoptosis both in cultured cells and in animal model. Meanwhile, silenced PCAT-1 exerted the opposite function. Additionally, PCAT-1 knockdown sensitized MM cells to bortezomib (Bort). Inhibitor of PCAT-1 combination with Bort exhibited a more effective inhibitory effect on MM cells compared with negative control or Bort alone. Further mechanism exploration via protein chips, Go and KEGG pathway analysis along with immunoblot analysis revealed that PCAT-1 facilitated cell growth and drug resistance via the p38 and JNK MAPK pathways. This study identified a novel lncRNA-associated mechanism underlying MM carcinogenesis, and provided clinicians with a promising therapeutic target in MM.

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