LncRNA KCNQ1OT1 accelerates fracture healing via modulating miR‐701‐3p/FGFR3 axis

Chen, Lang; Xiong, Yuan; Yan, Chenchen; Zhou, Wu; Endo, Yori; Xue, Hang; Hu, Yiqiang; Hu, Liangcong; Leng, Xingzhu; Liu, Jing; Lin, Ze; Mi, Bobin; Liu, Guohui

doi:10.1096/fj.201901864rr

Cited by 38 publications

(30 citation statements)

References 32 publications

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“…LncRNA KCNQ1OT1 promotes ovarian cancer progression by upregulating CAPN10 expression through sponging of miR-142-5p [26]. Moreover, lncRNA KCNQ1OT1 promotes osteoblast proliferation, migration, and survival by sponging miR-701-3p and upregulating FGFR3 [27]. However, the role of lncRNA KCNQ1OT1 in tumor glycolysis has not been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA KCNQ1OT1 promotes colorectal carcinogenesis by enhancing aerobic glycolysis via hexokinase-2

Chen

Wei

Wang

et al. 2020

Aging

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In this study, we investigated the mechanistic role and prognostic significance of the long coding RNA (lncRNA) KCNQ1OT1 in colorectal cancer (CRC). KCNQ1OT1 levels were significantly higher in CRC tissues than adjacent normal colorectal tissues (n=79). High KCNQ1OT1 expression correlated with poorer prognosis in CRC patients. KCNQ1OT1-silenced CRC cells showed reduced proliferation, colony formation, extracellular acidification, and lactate and glucose secretion. This suggests KCNQ1OT1 promotes CRC cell proliferation by increasing aerobic glycolysis. RNA pull-down assays with biotinylated KCNQ1OT1 followed by mass spectrometry analysis showed that KCNQ1OT1 directly binds to hexokinase 2 (HK2). This was confirmed by RNA immunoprecipitation assays using anti-hexokinase 2 antibody. HK2 protein levels were reduced in KCNQ1OT1 knockdown CRC cells, but were restored by treatment with the proteasomal inhibitor MG132. KCNQ1OT1 knockdown CRC cells also showed higher ubiquitinated-HK2 levels, suggesting KCNQ1OT1 enhances aerobic glycolysis by stabilizing HK2. HK2 overexpression in KCNQ1OT1 knockdown CRC cells restored proliferation and aerobic glycolysis. KCNQ1OT1 levels correlated positively with HK2 expression and prognosis in CRC patients. These findings show that KCNQ1OT1 promotes colorectal carcinogenesis by increasing aerobic glycolysis through HK2.

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Section: Introductionmentioning

confidence: 99%

Long noncoding RNA KCNQ1OT1 promotes colorectal carcinogenesis by enhancing aerobic glycolysis via hexokinase-2

Chen

Wei

Wang

et al. 2020

Aging

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“…The activation of EIF2AK3 can in turn stimulate phosphorylation of EIF2A, leading to increased ATF4 expression, which plays a central role in osteoblast differentiation [32,33]. Indeed, several studies have previously demonstrated that BMP2 plays a regulatory role in various biological processes [34][35][36]. For example, one group found that a BMP activity gradient is essential for normal dorsoventral patterning during gastrulation [37].…”

Section: Discussionmentioning

confidence: 99%

The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation

Xiong¹,

Chen²,

Yan³

et al. 2020

Int. J. Biol. Sci.

Self Cite

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The roles of long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs) as regulators of mRNA expression in various diseases have recently been reported. Osteoblast differentiation is the vital process which mediates bone formation and fracture healing. In present study, we found microRNA-6979-5p (miR-6979-5p) to be the most differentially expressed miRNA between normal bone and calluses of mice, and overexpression of miR-6979-5p was negatively associated with osteoblast differentiation. Through luciferase assays, we found evidence that bone morphogenetic protein 2 (BMP2) is a miR-6979-5p target gene that positively regulates osteoblast differentiation. We further identified the lncRNA Rhno1 as a competing endogenous RNA (ceRNA) of miR-6979-5p, and we verified that it was able to influence osteoblast differentiation both in vitro and in vivo. In summary, our data indicates that the lncRNA Rhno1/miR-6979-5p/BMP2 axis is a significant regulatory mechanism controlling osteoblast differentiation, and it may thus offer a novel therapeutic strategy for fracture healing.

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“…Emerging evidence of lncRNA KCNQ10T1 involvement in osteogenic processes have encouraged Chen and his group [39] to explore the role of this lncRNA during osteoblast migration, proliferation and survival, and, therefore, fracture healing. A study about the activity of lncRNA KCNQ10T1 in MC3T3-E1 cells showed that its knockdown leads to cell proliferation suppression with respect to cells with a normal expression of lncRNA KCNQ10T1.…”

Section: Lncrnas As Positive Regulatorsmentioning

confidence: 99%

The Involvement of Long Non-Coding RNAs in Bone

Aurilia

Donati

Palmini

et al. 2021

IJMS

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A harmonious balance between osteoblast and osteoclast activity guarantees optimal bone formation and resorption, pathological conditions affecting the bone may arise. In recent years, emerging evidence has shown that epigenetic mechanisms play an important role during osteoblastogenesis and osteoclastogenesis processes, including long non-coding RNAs (lncRNAs). These molecules are a class of ncRNAs with lengths exceeding 200 nucleotides not translated into protein, that have attracted the attention of the scientific community as potential biomarkers to use for the future development of novel diagnostic and therapeutic approaches for several pathologies, including bone diseases. This review aims to provide an overview of the lncRNAs and their possible molecular mechanisms in the osteoblastogenesis and osteoclastogenesis processes. The deregulation of their expression profiles in common diseases associated with an altered bone turnover is also described. In perspective, lncRNAs could be considered potential innovative molecular biomarkers to help with earlier diagnosis of bone metabolism-related disorders and for the development of new therapeutic strategies.

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LncRNA KCNQ1OT1 accelerates fracture healing via modulating miR‐701‐3p/FGFR3 axis

Cited by 38 publications

References 32 publications

Long noncoding RNA KCNQ1OT1 promotes colorectal carcinogenesis by enhancing aerobic glycolysis via hexokinase-2

Long noncoding RNA KCNQ1OT1 promotes colorectal carcinogenesis by enhancing aerobic glycolysis via hexokinase-2

The lncRNA Rhno1/miR-6979-5p/BMP2 Axis Modulates Osteoblast Differentiation

The Involvement of Long Non-Coding RNAs in Bone

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