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

Abstract

Thyroid carcinoma is the most widespread malignancy in endocrine system with the increasing incidence. Despite of the advanced approaches to the management of thyroid carcinoma, the therapeutic effects remain unpleasant largely due to the radiosensitivity of thyroid carcinoma cells. LncRNAs play important part in the tumorigenesis and development, especially in the radiosensitivity of tumor cells. However, their roles in thyroid carcinoma still needed to be explored deeply. The purpose of our research is to inspect the possible biological role and regulation mechanism of LINC00511 desirable for therapies of thyroid carcinoma patients. In the present study, LINC00511 was significantly overexpressed in thyroid carcinoma and its silencing boosted radiosensitivity of thyroid carcinoma cells. Then we unveiled that LINC00511 regulated JAK2/STAT3 signaling pathway which was resistant to radiation treatment. Besides, TAF1 modulated JAK2 at transcriptional level. Moreover, LINC00511 bound to TAF1 and further promoted JAK2 expression. In conclusion, rescue experiments verified that the radiosensitivity of thyroid carcinoma cells was attributed to LINC00511/TAF1/JAK2/STAT3 axis. The current paper investigated the underlying mechanism of LINC00511 and set a new therapeutic direction for the therapy of thyroid carcinoma.

Long Intergenic Non-protein Coding RNA 511 in Cancers

“…LINC00511 shows cancer promoting activity because it was shown that LINC00511 is up-expressed in many cancers and related to several features of cancer, such as proliferation (Sun et al, 2016 ; Li et al, 2018 ; Lu et al, 2018 ; Deng et al, 2019 ; Liu et al, 2019 ; Mao et al, 2019 ; Yu et al, 2019 ; Zhang J. et al, 2019 ; Zhu et al, 2019 ), apoptosis (Sun et al, 2016 ; Li et al, 2018 ; Deng et al, 2019 ; Mao et al, 2019 ; Wang R. P. et al, 2019 ; Zhang J. et al, 2019 ; Zhu et al, 2019 ), invasion (Sun et al, 2016 ; Lu et al, 2018 ; Mao et al, 2019 ; Quan et al, 2019 ; Wang R. P. et al, 2019 ; Yu et al, 2019 ; Zhu et al, 2019 ), radio-resistance (Chen et al, 2019 ; Liu et al, 2019 ), migration (Sun et al, 2016 ; Mao et al, 2019 ; Wang R. P. et al, 2019 ; Yu et al, 2019 ; Zhu et al, 2019 ), drug resistance (Mao et al, 2019 ), metastasis (Deng et al, 2019 ; Zhu et al, 2019 ), and growth (Sun et al, 2016 ; Deng et al, 2019 ; Wang R. P. et al, 2019 ). High LINC00511 expression is significantly correlated with TNM classification, lymph node metastasis, and short OS among patients with clear cell renal cell carcinoma (Deng et al, 2019 ) and NSCLC (Zhu et al, 2019 ).…”

LINC00511 as a prognostic biomarker for human cancers: a systematic review and meta-analysis

“…These mechanistic studies revealed that LINC00511 could act at transcriptional and post-transcriptional level. Moreover, LINC00511 was found to interact with a variety of signaling pathways including JAK2/STAT3 [ 45 ], Wnt/β-catenin [ 46 ], and PTEN/AKT/FOXO1 [ 47 ], in the pathogenesis of cancers.…”

Prognostic significance of long intergenic non-protein-coding RNA 511expression in malignant tumors

“…[ 14 – 16 ] Jiang et al [ 36 ] also suggested that silencing LINC00511 would suppress the proliferation, migration, and epithelial-mesenchymal transition of lung cancer cells by modulating the PTEN/AKT/FOXO1 axis. Moreover, Li et al [ 37 ] found that overexpression of LINC00511 enhanced the proliferation and invasion of glioma cells through inhibition of miR-124-3p and concomitant upregulation of cyclin D2. [ 37 ] In OC, LINC00511 was found to interact with enhancer of zeste homologue 2 to repress P21 expression, thereby augmenting the viability and invasive ability of cancer cells.…”

“…Moreover, Li et al [ 37 ] found that overexpression of LINC00511 enhanced the proliferation and invasion of glioma cells through inhibition of miR-124-3p and concomitant upregulation of cyclin D2. [ 37 ] In OC, LINC00511 was found to interact with enhancer of zeste homologue 2 to repress P21 expression, thereby augmenting the viability and invasive ability of cancer cells. [ 16 ] Yu et al [ 10 ] and Mao et al [ 9 ] also demonstrated that LINC00511 could promote the proliferation, migration, invasion, and resistance to paclitaxel in CC cells by upregulating matrix metalloproteinase-9, P-glycoprotein, Bcl-2, and a multidrug resistance protein.…”

“…In pancreatic cancer, overexpression of LINC00511 could significantly contribute to tumor cell proliferation, migration, invasion, and angiogenesis via the miR-29b-3p / vascular endothelial growth factor A axis. [ 17 ] In thyroid cancer, Chen et al [ 37 ] revealed that LINC00511 could bind to TATA-box binding protein-associated factor 1 to activate Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, which remarkably decreased the radio-sensitivity of malignant cells. In renal cell cancer cells, Deng et al [ 25 ] found that LINC00511 was capable of promoting the proliferation, colony formation, in vitro invasion, and in vivo tumor growth, as well as inhibit apoptosis of cancer cells, by repressing the miR-625 and consequently upregulating CCND1.…”