LincRNA‐p21 enhances the sensitivity of radiotherapy for gastric cancer by targeting the β‐catenin signaling pathway

Abstract

Long noncoding RNAs (lncRNAs) are a large and diverse class of transcribed RNA molecules with a length of more than 200 nucleotides that modulate the gene expression at the posttranscriptional or transcriptional level. LncRNAs played crucial roles in many biological processes, such as cell proliferation, metastasis, and migraton. In this study, we evaluated the role of lincRNA‐p21 in the gastric cancer (GC). We demonstrated that the expression level of lincRNA‐p21 was downregulated in the GC tissues and cell lines. Moreover, ectopic expression of lincRNA‐p21 suppressed the GC cell growth, cell cycle, and migration. Furthermore, we demonstrated that the X‐ray increased the expression level of lincRNA‐p21 in both the HCG‐27 and SGC7901 cells and elevated expression of lincRNA‐p21 increased the radiotherapy sensitivity of the GC cell. In addition, we showed that ectopic expression of lincRNA‐p21 suppressed the β‐catenin and c‐myc expression. Overexpression of lincRNA‐p21 inhibited the GC cell proliferation and increased the radiosensitivity of GC cells by regulating the β‐catenin signaling pathway. These data suggested that lincRNA‐p21 acted as a tumor suppressor gene in the development of GC.

Non-Coding RNAs in Cancer Radiosensitivity: MicroRNAs and lncRNAs as Regulators of Radiation-Induced Signaling Pathways

“…Levels of β-catenin and its target genes, c-MYC and Cyclin D1, were also downregulated upon lincRNA-p21 overexpression, as well as upon IR in CRC [100]. Inhibition of the β-catenin pathway abolished the effects of lincRNA-p21 overexpression on cell proliferation and radiosensitivity in gastric cancer cells [99]. This supports the role of lincRNA-p21 in promoting radiosensitivity by inhibiting the Wnt/β-catenin pathway.…”

“…A handful of lncRNAs have been linked to IR response by regulating the Wnt/β-catenin pathway. lincRNA-p21 was downregulated in gastric cancer and CRC cells and tissues [99,100]. Ectopic overexpression of lincRNA-p21 enhanced radiosensitivity and inhibited the Wnt/β-catenin pathway in both tumor types.…”

Knockdown of LINC00511 promotes radiosensitivity of thyroid carcinoma cells via suppressing JAK2/STAT3 signaling pathway

“…Furthermore, it has been elucidated that lncRNAs modulate the radioresistance of tumors through modulating gene expression, 32 and signaling pathways against radiotherapy in tumors. 21,33,34 Thereupon, we attempted to explore the association between LINC00511 and JAK2/STAT3 signaling pathway. Our paper displayed that LINC00511 regulated JAK2/ STAT3 signaling pathway and JAK2 expression was upregulated when given 4Gy irradiation in thyroid carcinoma, where the association of JAK2/STAT3 signaling pathway with radioresistance was probed for the first time.…”

“…The Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway is constitutively stimulated at high level, and regulates the expression of various genes as well as physiological functions in tumors. [17][18][19] Despite multiple reports have claimed the radioresistant effect of signaling pathways on tumors, 20,21 the function of JAK3/ STAT3 signaling pathway in the radioresistance of carcinomas is still controversial.…”

Research Progress on Long Non-Coding RNA and Radiotherapy

“…In addition, they showed that ectopic expression of lincRNA-p21 suppressed β-catenin and c-myc expression. Overexpression of lincRNA-p21 inhibited the GC cell proliferation and increased the radiosensitivity of GC cells by regulating the Wnt/β-catenin signaling pathway, the activation of which is one of the most common features of GC [113].…”