hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2

Lee, Woo Joo; Shin, Chang Hoon; Ji, Haein; Jeong, Seong Dong; Park, Mi-So; Won, Hong-Hee; Pandey, Poonam R; Tsitsipatis, Dimitrios; Gorospe, Myriam; Kim, Hyeon Ho

doi:10.1038/s41419-021-03575-1

Cited by 21 publications

(14 citation statements)

References 38 publications

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“…As previously reported, we found that hnRNPK upregulates LINC00263 by directly binding and enhancing its stability (Lee et al, 2021). Although LINC00162 is also regulated by hnRNPK, no molecular interaction was observed, indicating that hnRNPK indirectly regulates LINC00162 levels.…”

Section: Discussionsupporting

confidence: 84%

“…To search for hnRNPK-regulated lincRNAs, RNA sequencing was performed using total RNA isolated from HeLa cells, transfected with either control or hnRNPK siRNA (Lee et al, 2021). An analysis of the RNA sequencing data (Figure S1a-c) found that the expression of LINC00162 was reduced in hnRNPK-silenced HeLa cells (Figure 1a,b).…”

Section: Expression Of Linc00162 Is Positively Regulated By Hnrnpkmentioning

confidence: 99%

“…We have investigated the molecular mechanism by which heterogeneous nuclear ribonucleoprotein K (hnRNPK) promotes the malignant properties of cancer. In previous report, two intergenic noncoding RNAs (long intergenic noncoding RNAs [lincRNAs) were identified as the target of hnRNPK (Lee et al, 2021). LINC00263 strengthens the proliferative and metastatic abilities by sponging miR‐148a, thus increasing the expression of calpain 2.…”

Section: Introductionmentioning

confidence: 99%

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LINC00162 regulates cell proliferation and apoptosis by sponging PAQR4‐targeting miR‐485‐5p

Lee

Jeong

et al. 2022

Journal Cellular Physiology

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Growing evidence indicates that long intergenic noncoding RNAs play an important role in cancer progression by affecting gene regulation at the transcriptional and posttranscriptional levels. Recent studies have shown that long intergenic noncoding RNA functions as a competitive endogenous RNA, which can interact with and mitigate the function of microRNA. In this study, we investigated the molecular mechanism by which LINC00162 regulates cell proliferation and apoptotic cell death. By analyzing RNA sequencing data, LINC00162 was identified to be a target of heterogeneous nuclear ribonucleoprotein K (hnRNPK). HnRNPK positively regulated LINC00162 expression through p38 mitogen‐activated protein kinase. Lowering the level of either hnRNPK or LINC00162 decreased proliferation and colony formation while it increased apoptotic cell death. Small RNA sequencing followed by the antisense oligonucleotide pulldown, revealed that LINC00162 interacts directly with miR‐485‐5p which exhibited tumor‐suppressing effects by suppressing cell proliferation and colony formation, and increasing apoptotic cell death. Through the bioinformatic approaches, progestin and adipoQ receptor 4 (PAQR4) was selected as a common target of LINC00162 and miR‐485‐5p. miR‐485‐5p decreased the expression of PAQR4 by directly binding to the 3′‐untranslated region of PAQR4 messenger RNA. Knockdown of hnRNPK and LINC00162 increased the level of functional miR‐485‐5p, indicating that LINC00162 may compete for miR‐485‐5p, thereby derepressing PAQR4 expression. Overexpression of either hnRNPK or LINC00162, or inhibition of miR‐485‐5p, protected cells against etoposide‐induced apoptotic death. Our findings demonstrate that a regulatory paradigm implicating hnRNPK, LINC00162, miR‐485‐5p, and PAQR4 plays an important role in cell proliferation and apoptosis, and is a promising target for cancer therapeutics.

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Section: Discussionsupporting

confidence: 84%

Section: Expression Of Linc00162 Is Positively Regulated By Hnrnpkmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LINC00162 regulates cell proliferation and apoptosis by sponging PAQR4‐targeting miR‐485‐5p

Lee

Jeong

et al. 2022

Journal Cellular Physiology

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“…The dual luciferase reporter assay was performed as previously reported [ 28 , 29 ] and was used to analyze whether miR-100-5p directly targets mTOR to control its expression. Wild-type mTOR (mTOR-WT) 3′-UTR containing the miR-100-5p potential binding site (5' TACGGGT 3') was inserted into the pmirGLO luciferase vector (Promega Corporation).…”

Section: Methodsmentioning

confidence: 99%

Exosomes derived from stem cells of human deciduous exfoliated teeth inhibit angiogenesis in vivo and in vitro via the transfer of miR-100-5p and miR-1246

Zhang

et al. 2022

Stem Cell Res Ther

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Background Anti-angiogenic therapy has been shown to be a promising strategy for anti-tumor treatment. Increasing evidence indicates that tumor angiogenesis is affected by exosomes that are secreted by mesenchymal stem cells (MSCs), but whether exosomes derived from MSCs suppress or promote angiogenesis remain paradoxical. The purpose of this study focused on understanding the potential role of exosomes derived from stem cells of human deciduous exfoliated teeth (SHED-Exos) in regulating angiogenesis and the underlying molecular mechanism. Methods Exosomes were isolated from supernatants of SHED cells using an exosome purification kit and were characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. Cell Counting Kit-8, flow cytometric assays, western blots, wound healing and transwell migration assays were performed to characterize the roles of SHED-Exos on cell proliferation, apoptosis and migration of human umbilical vein endothelial cells (HUVECs). The anti-angiogenic activity of SHED-Exos was assessed via a tube formation assay of endothelial cells and angiogenesis-related factors were analyzed by western blotting. In vivo, we used the chick chorioallantoic membrane (CAM) assay and an oral squamous cell carcinoma (OSCC) xenograft transplantation model with nude mice that received multi-point injections at three-day intervals to evaluate the effects on angiogenesis. Furthermore, the sequencing of microRNAs (miRNAs) in SHED-Exos was performed to investigate the underlying anti-angiogenic mechanism. Results The results showed that SHED-Exos inhibit cell proliferation and migration and induce apoptosis in HUVECs. SHED-Exos suppress the tube-like structure formation of HUVECs in vitro. SHED-Exos downregulate several angiogenesis-related factors, including VEGFA, MMP-9 and ANGPT1. In vivo, the chick CAM assay verified that treatment with SHED-Exos inhibits micro-vascular formation, and importantly, significantly reduces the micro-vascular formation of tumors generated from xenografted OSCC cells, which was associated with the inhibition of tumor growth in vivo. Mechanistically, our data suggested that SHED-Exos are enriched with miR-100-5p and miR-1246 and are transferred to endothelial cells, which results in decreased tube formation via the down-regulation of VEGFA expression. Conclusions These results demonstrate that SHED-Exos inhibit angiogenesis in vitro and in vivo, which suggests that SHED-Exos could potentially serve as a novel and effective therapeutic approach for anti-angiogenic treatment.

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“…Previous study has confirmed that miR-147a suppresses malignant capabilities, including invasiveness, proliferation, and clonogenicity, via targeting calpain 2. 14 Moreover, miR-147a upregulation suppressed mouse lung epithelial TC-1 cells through mitigating inflammation and apoptosis. Mechanistically, miR-147a inhibited the activation of NF-κB signaling via directly targeting NF-κB activating protein.…”

Section: Introductionmentioning

confidence: 99%

Notoginsenoside R1 alleviates high glucose‐induced inflammation and oxidative stress in HUVECs via upregulating miR‐147a

Huang

2021

The Kaohsiung J of Med Scie

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Endothelial dysfunction in atherosclerotic cardiovascular diseases has become one of the main characteristics in patients with diabetes mellitus, which is usually caused by abnormal inflammation and oxidative stress response. Presently, we focused on the role of Notoginsenoside R1 (NR1), a major component isolated from Panax notoginseng, in endothelial dysfunction caused by high glucose (HG). Human umbilical vein endothelial cells (HUVECs) were treated with HG and then dealt with NR1. Cell counting kit-8 assay and 5-bromo-2 0 -dexoyuridine assay were conducted to examine cell proliferation and viability. Flow cytometry was used to measure apoptosis. The angiogenesis of HUVECs was determined by tube formation assay. Moreover, the expressions of miR-147a, inflammatory cytokines (TNF-α, IL-6, and IL-10) and oxidative stress markers malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. The protein levels of MyD88/TRAF6/NF-κB axis, Bax, Bcl2, and Caspase3 were detected by Western blot. Furthermore, gain and loss of functional assays of miR-147a were performed to verify the role of miR-147a in NR1-mediated effects. Our data confirmed that NR1 (at 10-40 μM) reduces HG-induced HUVECs proliferation and viability inhibition, mitigates apoptosis, and enhances tube formation ability. Meanwhile, NR1 inhibited oxidative stress and inflammatory response and blocked the activation of the MyD88/TRAF6/NF-κB pathway induced by HG. In addition, NR1 promoted the expression of miR-147a, which targeted MyD88. Overexpression of miR-147a markedly inactivated MyD88/ TRAF6/NF-κB pathway, while the miR-147a inhibitors reversed NR1-mediated protective effect in HG-induced HUVECs through activating MyD88/TRAF6/NF-κB pathway. In conclusion, NR1 relieves HG-induced endothelial cell injury by downregulating the MyD88/TRAF6/NF-κB pathway via upregulating miR-147a.

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hnRNPK-regulated LINC00263 promotes malignant phenotypes through miR-147a/CAPN2

Cited by 21 publications

References 38 publications

LINC00162 regulates cell proliferation and apoptosis by sponging PAQR4‐targeting miR‐485‐5p

LINC00162 regulates cell proliferation and apoptosis by sponging PAQR4‐targeting miR‐485‐5p

Exosomes derived from stem cells of human deciduous exfoliated teeth inhibit angiogenesis in vivo and in vitro via the transfer of miR-100-5p and miR-1246

Notoginsenoside R1 alleviates high glucose‐induced inflammation and oxidative stress in HUVECs via upregulating miR‐147a

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