MicroRNA let-7g inhibited hypoxia-induced proliferation of PASMCs via G0/G1 cell cycle arrest by targeting c-myc

Zhang, Weifang; Xiong, You-Wen; Zhu, Tiantian; Xiong, Aizhen; Bao, Huihui; Cheng, Xiaoshu

doi:10.1016/j.lfs.2016.11.020

Cited by 28 publications

(25 citation statements)

References 31 publications

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“…Let-7 family members also participate in PH. A previous study reported that let-7 g inhibited PASMCs proliferation in HPH [55]. Moreover, the reduced expression of let-7b increased the expression of ET-1 and thus affected PASMCs and PAECs proliferation in chronic thromboembolic pulmonary hypertension [56].…”

Section: Discussionmentioning

confidence: 99%

LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension

Yan

et al. 2018

Respir Res

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BackgroundPulmonary arterial hypertension (PAH) is related to inflammation, and the lncRNA H19 is associated with inflammation. However, whether PDGF-BB-H19-let-7b-AT1R axis contributes to the pathogenesis of PAH has not been thoroughly elucidated to date. This study investigated the role of H19 in PAH and its related mechanism.MethodsIn the present study, SD rats, C57/BL6 mice and H19−/− mice were injected with monocrotaline (MCT) to establish a PAH model. H19 was detected in the cytokine-stimulated pulmonary arterial smooth muscle cells (PASMCs), serum and lungs of rats/mice. H19 overexpression and knockdown experiments were also conducted. A dual luciferase reporter assay was used to explore whether let-7b is a sponge miRNA of H19, and AT1R is a novel target of let-7b. A CCK-8 assay and flow cytometry were used to analyse cell proliferation.ResultsThe results showed that H19 was highly expressed in the serum and lungs of MCT-induced rats/mice, and H19 was upregulated by PDGF-BB in vitro. H19 upregulated AT1R expression via sponging miRNA let-7b following PDGF-BB stimulation. AT1R is a novel target of let-7b. Moreover, the overexpression of H19 and AT1R could facilitate PASMCs proliferation in vitro. H19 knockout protected mice from pulmonary artery remodeling and PAH following MCT treatment.ConclusionOur study showed that H19 is highly expressed in MCT-induced rodent lungs and upregulated by PDGF-BB. The H19-let-7b-AT1R axis contributed to the pathogenesis of PAH by stimulating PASMCs proliferation. The H19 knockout had a protective role in the development of PAH. H19 may be a potential tar-get for the treatment of PAH.

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Section: Discussionmentioning

confidence: 99%

LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension

Yan

et al. 2018

Respir Res

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“…Various studies have demonstrated a role for miRNAs (Cui et al, ; Hao et al, ; Lulla et al, ; Rao, He, He, Guo, & Kong, ; X. Zhang et al, ), and and in some cases for let‐7 family (Iwasaki et al, ; W.‐F. Zhang, Xiong, Zhu, & Xiong, ; Zhu et al, ), in suppression of the cell cycle, mainly by induction of G1 cell cycle arrest. In the present study, we analyzed the effects of irradiation at different cell‐cycle phases by measuring the percentage of cells.…”

Section: Discussionmentioning

confidence: 99%

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi

Afshar

Amini

et al. 2018

Journal Cellular Physiology

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Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let‐7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let‐7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF‐1R is a direct target of the let‐7e member. Consistent with this, we identified that increased levels of let‐7e in CRC cells reduced IGF‐1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let‐7e by targeting the IGF‐1R signaling pathway might serve as therapeutics in anticancer therapy.

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“…Primary PASMCs were obtained from rat pulmonary arteries as previous described [14]. Cells were then cultured for 3–5 days in a humidified incubator with 5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-214-3p Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ARHGEF12

Xing

et al. 2019

Med Sci Monit

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Background miR-214-3p has been found to inhibit proliferation and migration in cancer cells. The objective of this study was to determine whether ARHGEF12 is involved in miR-214-3p-mediated suppression of proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Material/Methods PASMCs were cultured under normoxia or hypoxia. miR-214-3p mimics or inhibitors were transiently transfected into PASMCs. Proliferation, apoptosis, and migration of PASMCs were evaluated using MTT assay, flow cytometry, and Boyden chamber apparatus. Western blot analysis was used to examine expression of Rho guanine nucleotide exchange factor 12 (ARHGEF12), c-fos, c-jun, and caspase-3. Luciferase reporter assay was used to test the direct regulation of miR-214-3p on the 3′-untranslated region (UTR) of ARHGEF12. Results miR-214-3p was significantly upregulated in hypoxia-treated PASMCs. Knockdown of miR-214-3p significantly attenuated hypoxia-induced proliferation and migration in PASMCs and promoted apoptosis, whereas this effect was aggravated by overexpression of miR-214-3p. In addition, dual-luciferase reporter assay demonstrated that ARHGEF12 is a direct target gene of miR-214-3p. The protein levels of ARHGEF12 were downregulated after knockdown of miR-214-3p in PASMCs. Rescue experiment results indicated that decreased proliferation of PASMCs resulted from knockdown of miR-214-3p were partially reversed by silencing of ARHGEF12 by siRNA. Furthermore, knockdown of miR-214-3p reduced expression of c-jun and c-fos, but increased expression of caspase-3 in PASMCs under hypoxia. Conclusions In conclusion, these results indicate that miR-214-3p acts as a novel regulator of hypoxia-induced proliferation and migration by directly targeting ARHGEF12 and dysregulating c-jun and c-fos in PASMCs, and may be a potential therapeutic target for treating pulmonary hypertension.

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MicroRNA let-7g inhibited hypoxia-induced proliferation of PASMCs via G0/G1 cell cycle arrest by targeting c-myc

Cited by 28 publications

References 31 publications

LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension

LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT1R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

MicroRNA-214-3p Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ARHGEF12

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