Long non-coding RNA THOR promotes human osteosarcoma cell growth in vitro and in vivo

Chen, Wangzhen; Chen, Meikai; Xu, Yifan; Chen, Xuerong; Zhou, Ping; Zhao, Xiaofeng; Pang, Fei; Liang, Wenqing

doi:10.1016/j.bbrc.2018.04.019

Cited by 40 publications

(35 citation statements)

References 21 publications

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“…Significantly reduced cell proliferation in the hTHOR −/− cells Previous studies indicated that the lncRNA THOR, representative of cancer/testis lncRNAs, plays a positive role in cancer cell proliferation [10][11][12][13] . To explore the function of the lncRNA THOR in cancer cells, the cellular distribution of the lncRNA THOR was analysed by qRT-PCR and RNA-FISH assay.…”

Section: Resultsmentioning

confidence: 97%

“…Dysregulated expression of lncRNA THOR has been reported to modulate the progression of various types of cancers, such as melanoma, non-small cell lung cancer, osteosarcoma and renal cell carcinoma [10][11][12] . Currently, the molecular mechanisms of cancer/testis lncRNAs in cancer metastasis are largely unknown and need to be fully elucidated [10][11][12][13] . family (YTHDF1-3) and the nuclear member YTH domain containing 1 (YTHDC1) 1,[31][32][33][34][35] .…”

Section: Introductionmentioning

confidence: 99%

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A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

Yao

et al. 2020

Cell Death Dis

100

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Previous studies have revealed the critical roles of the N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in cancers, but the relationship between the oncogenic role of the lncRNA THOR (a representative of cancer/testis lncRNAs) and m6A modification remains unclear. Here, we show that the internal m6A modification of the lncRNA THOR via an m6A-reader-dependent modality regulates the proliferation of cancer cells. Our findings demonstrated that the loss of the lncRNA THOR inhibits the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In addition, m6A is highly enriched on lncRNA THOR transcripts, which contain GA (m6A) CA, GG (m6A) CU, and UG (m6A) CU sequence motifs. RIP-qRT-PCR and RNA pull-down assay results revealed that the specific m6A readers YTHDF1 and YTHDF2 can read the m6A motifs and regulate the stability of the lncRNA THOR (stabilization and decay). These m6A-dependent RNA-protein interactions can maintain the oncogenic role of the lncRNA THOR. Collectively, these findings highlight the critical role of the m6A modification in oncogenic lncRNA THOR and reveal a novel long non-coding RNA regulatory mechanism, providing a new way to explore RNA epigenetic regulatory patterns in the future. Recently, the new field of "RNA epigenetics" has been booming 14,15 , and N6-methyladenosine (m6A) has been identified as a post-transcriptional regulatory mark in multiple RNA species, including messenger RNAs (mRNAs) 1,2,16 , transfer RNAs (tRNAs) 3,4,17-20 , ribosomal RNAs (rRNAs) 21 , small nuclear RNA 22 , small non-coding RNAs (sncRNAs) 23 , and lncRNAs 16,24. It has been reported that the m6A RNA modification is conferred by methyltransferases (writers), such as methyltransferaselike 3 (METTL3), forming the catalytic core of the m6A methyltransferase complex 25-28. In addition, the biological function of m6A is mediated through the recognition of the m6A site by m6A "readers" 1,29,30 , such as the YT521-B homology (YTH) family, including YTH domain

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

Yao

et al. 2020

Cell Death Dis

100

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“…Overexpression of lncRNA PVT1 is correlated with leukaemic cell proliferation in acute promyelocytic leukaemia . Notably, several studies have shown that lncRNAs play critical roles in OS progression, such as lncRNA THOR promotes human OS cells growth in vitro and in vivo, and LncRNA DICER1‐AS1 promotes the proliferation, invasion and autophagy of OS cells via miR‐30b/ATG5 . However, the roles and mechanisms of lncRNAs in OS progression are still confused.…”

Section: Discussionmentioning

confidence: 99%

LncRNA B4GALT1‐AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity

Wang

et al. 2018

Cell Proliferation

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“…Human OS tumor tissues and the matched surrounding normal bone tissues from a total of twelve (12) written-informed OS patients were provided by Dr. Liang at Zhejiang University [ 29 ]. Tissues were incubated with the described lysis buffer [ 29 ], stored in liquid nitrogen. The protocols of the study were approved by Ethics committee of Soochow University.…”

Section: Methodsmentioning

confidence: 99%

p38γ overexpression promotes osteosarcoma cell progression

Shi

Cheng

Yin

et al. 2020

Aging

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Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. Recent studies demonstrate that p38 gamma (p38γ) phosphorylates retinoblastoma (Rb) to promote cyclin expression, cell-cycle entry and tumorigenesis. Studying the potential function of p38γ in human OS, we show that p38 γ mRNA and protein expression are significantly elevated in OS tissues and OS cells, whereas its expression is relatively low in normal bone tissue and in human osteoblasts/osteoblastic cells. Knockdown of p38γ in established (U2OS) and primary human OS cells potently inhibited cell growth, proliferation, migration and invasion, while promoting cell apoptosis. Furthermore, CRISPR/Cas9-induced p38γ knockout inhibited human OS cell progression in vitro . Conversely, ectopic overexpression of p38γ in primary human OS cells augmented cell growth, proliferation and migration. Signaling studies show that retinoblastoma (Rb) phosphorylation and cyclin E1/cyclin A expression were decreased following p38γ shRNA knockdown and knockout, but increased after ectopic p38γ overexpression. Collectively, these results show that p38γ overexpression promotes human OS cell progression.

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Long non-coding RNA THOR promotes human osteosarcoma cell growth in vitro and in vivo

Cited by 40 publications

References 21 publications

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

A novel N6-methyladenosine (m6A)-dependent fate decision for the lncRNA THOR

LncRNA B4GALT1‐AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity

p38γ overexpression promotes osteosarcoma cell progression

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