Hypoxia‐responsive miR‐124 and miR‐144 reduce hypoxia‐induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing <scp>PIM</scp>1

Gu, Hongtao; Liu, Mingzhu; Ding, Changmao; Wang, Xin; Wang, Rui; Wu, Xinyu; Fan, Ruitai

doi:10.1002/cam4.664

Cited by 67 publications

(37 citation statements)

References 23 publications

(37 reference statements)

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“…reported that knockdown of Pim1 significantly attenuated hypoxia-induced autophagy, whereas Pim1 overexpression markedly enhanced hypoxia-induced autophagy in prostate cancer cells [35]. We found that Pim1 overexpression enhanced autophagy and decreased apoptosis in vitro in NRVMs in the presence of hypoxia and H 2 O 2 .…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 50%

Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy

Zhu¹,

Wang²,

Sun³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Microvascular obstruction (MVO), an undesirable complication of percutaneous coronary intervention, is independently associated with adverse left ventricle remodeling and poor prognosis after acute myocardial infarction. Hypoxia and oxidative stress major roles in the pathophysiology of MVO. Pim1 serves an important protective role in the ischemic myocardium, but the underlying mechanisms remain poorly defined. Autophagy in early hypoxia or during moderate oxidative stress has been demonstrated to protect the myocardium. In this study, we investigated the association between the protective effect of Pim1 and autophagy after hypoxia and oxidative stress. Methods: Ventricular myocytes from neonatal rat heart (NRVMs) were isolated. NRVMs were exposed to hypoxia and H₂O₂. Rapamycin and 3-methyladenine (3-MA) were used as an activator and inhibitor of autophagy, respectively. pHBAd-Pim1 was transfected into NRVMs. We assessed cardiomyocyte apoptosis by Annexin V-FITC/PI flow cytometry. Autophagy was evaluated by mRFP-GFP-LC3 adenovirus infection by confocal microscopy. Western blotting was used to quantify apoptosis or autophagy protein (caspase-3, LC3, P62, AMPK, mTOR, ATG5) concentrations. Results: Autophagy and apoptosis in NRVMs significantly increased and peaked at 3 h and 6 h, respectively, after exposure to hypoxia and H₂O₂. The mTOR inhibitor rapamycin induced autophagy and decreased cardiomyocyte apoptosis, but the autophagy inhibitor 3-MA decreased autophagy and increased apoptosis at 3 h after exposure to hypoxia and H₂O₂. Pim1 levels in NRVMs increased at 3 h and decreased gradually after exposure to hypoxia and H₂O₂. Pim1 overexpression enhanced autophagy and decreased apoptosis. Pim1-induced promotion of autophagy is partly the result of activation of the AMPK/mTOR/ATG5 pathway after exposure to hypoxia and H₂O₂. Conclusion: Our results revealed that Pim1 overexpression prevented NRVMs from apoptosis via upregulating autophagy after exposure to hypoxia and oxidative stress, partly through activation of the AMPK/mTOR/ATG5 autophagy pathway.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 50%

Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy

Zhu¹,

Wang²,

Sun³

et al. 2018

Cell Physiol Biochem

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“…In these cancers, some established tumor suppressive genes were found to be the direct targets of miR-144, such as PTEN in nasopharyngeal carcinoma (Song et al, 2019), and ARID1A in clear cell renal cell carcinoma (Xiao et al, 2017). In prostate cancer, miR-144 was shown to enhance radiotherapy sensitivity and suppress hypoxia-induced autophagy by inhibiting PIM1 expression (Gu et al, 2016). Furthermore, miR-144 could decrease the proliferative ability and induce apoptosis in CRPC cells by targeting CEP55 (You and Zhang, 2018).…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis

et al. 2020

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Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.

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“…Moreover, they found that cisplatin, platinol chemotherapy (CDDP) might induce VEGF through miR-144 levels suppression in PrC cells, with cell autophagy inhibition. Another study by Gu H et al found that miR-124 and miR-144 directly targeted the 3 UTR of PIM1 and, via its downregulation, led to hypoxia-induced autophagy and increased radiosensitivity of PrC [122]. Zheng H et al determined that miR-144-3 prevents proliferation and leads to cell death in PrC by targeting CEP55 [123].…”

Section: Mir-144 In Prostate Cancermentioning

confidence: 99%

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Kooshkaki

Rezaei

Rahmati

et al. 2020

IJMS

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MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.Int. J. Mol. Sci. 2020, 21, 2578 2 of 23 of a mRNA molecule [3]. MiRNAs indicate a new perspective in the study of cancers. More than 50% of miRNA genes were discovered to be located within the genomic regions that are involved in cancers, suggesting their role in human cancer pathogenesis. In pathological conditions, MiRNAs can negatively regulate gene expression and they are associated with tumor growth, apoptosis, invasion, and metastasis. In the past, several studies have indicated the ability of miRNAs in the inhibition of tumors as a critical option for the improvement of cancer therapy [4,5]. Tumor activator miRNAs, called oncomiRs, are overexpressed in various cancers. On the contrary, suppressive tumor miRNAs are underexpressed [6][7][8]. Among several miRNAs assessed, miR-144s seem to have a role in several cancers. These miRNAs are located in the chromosomal region 17q11.2, being significantly destroyed in many types of cancers. The predicted stem-loop structure of miR-144s recognized by the miRBase (http://mirbase.org/) is shown in Figure 1A. The miR-144 hairpin gives rise to the "guide strand" miR-144-5p and the sister "passenger" strand miR-144-3p ( Figure 1B).

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Hypoxia‐responsive miR‐124 and miR‐144 reduce hypoxia‐induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1

Cited by 67 publications

References 23 publications

Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy

Pim1 Overexpression Prevents Apoptosis in Cardiomyocytes After Exposure to Hypoxia and Oxidative Stress via Upregulating Cell Autophagy

Long Non-coding RNA SNHG17 Promotes Cell Proliferation and Invasion in Castration-Resistant Prostate Cancer by Targeting the miR-144/CD51 Axis

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

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