TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA.

When cells are stressed, DNA from energy-producing mitochondria can leak out and drive inflammatory immune responses if not cleared. Cells employ a quality control system called autophagy to specifically degrade damaged components. We discovered that mitochondrial transcription factor A (TFAM)-a protein that binds mitochondrial DNA (mtDNA)-helps to eliminate leaked mtDNA by interacting with the autophagy protein LC3 through an autolysosomal pathway (we term this nucleoid-phagy). TFAM contains a molecular zip code called the LC3 interacting region (LIR) motif that enables this binding. Although mutating TFAM's LIR motif did not affect its normal mitochondrial functions, more mtDNA accumulated in the cell cytoplasm, activating inflammatory signalling pathways. Thus, TFAM mediates autophagic removal of leaked mtDNA to restrict inflammation. Identifying this mechanism advances understanding of how cells exploit autophagy machinery to selectively target and degrade inflammatory mtDNA. These findings could inform research on diseases involving mitochondrial damage and inflammation.

The value of dual time-point fluorine-18 fluorodeoxyglucose PET/computed tomography imaging in predicting lymph node metastasis in non-small cell lung cancer patients.

OBJECTIVE: The purpose of this study was to analyze the correlation between specified dual time-point fluorine-18 fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) imaging parameters and pathological characteristics in non-small cell lung cancer (NSCLC) patients. METHODS: This study retrospectively analyzed 47 patients with NSCLC. All patients underwent dual time-point 18F-FDG PET/CT imaging. We obtained the metabolic parameters, standardized uptake value (SUV) maximum, SUVmean, delayed standardized uptake value (DSUV) maximum, DSUVmean, delay index standardized uptake value (DISUV) maximum, and DISUVmean, of the primary tumor. The tumor size was measured by CT. All lymph nodes had a definite pathological diagnosis. We next evaluated the status of the lymph node metastases (LNM) and the correlations between metabolic parameters and clinical characteristics. Receiver operating characteristic curves were drawn for the prediction of LNM. RESULTS: We found that the DSUVmax, DISUVmax, DSUVmean, and tumor size were significantly related to LNM (P = 0.036, 0.009, and 0.049, respectively). Multivariate analysis revealed that tumor size and DISUVmax were independent risk factors for LNM in lung cancer patients. According to the receiver operating characteristic curve analysis, the optimal cutoff values for DISUVmax and tumor size were 0.33 and 2.8 cm, respectively. When these two parameters were combined, the area under the curve for predicting LNM in NSCLC was 0.768, and the sensitivity was 95.7% for predicting LNM in lung cancer patients. We further allocated the patients to three groups: the high-risk group (tumor size ≥ 2.8 cm, DISUVmax ≥ 0.33), the moderate-risk group (tumor size ≥ 2.8 cm, DISUVmax < 0.33, or tumor size < 2.8 cm, DISUVmax ≥ 0.33), and the low-risk group (tumor size < 2.8 cm, DISUVmax < 0.33). The rates of LNM were 70, 50, and 0%, respectively. CONCLUSION: Tumor size and DISUVmax are risk factors for predicting LNM, and they are more useful in combination. Compared with standard PET/CT imaging, dual time-point PET/CT imaging has added value in predicting LNM in NSCLC patients.

Impact factors of benefiting from initial 131 I ablation in patients with intermediate-risk differentiated thyroid carcinoma: a study based on a re-evaluation of therapeutic response.

OBJECTIVE: This study was carried out to confirm whether patients with intermediate-risk differentiated thyroid cancer (DTC) could benefit from initial 131 I ablation and to identify the factors that impacted the benefit. METHODS: We retrospectively assessed a cohort of 548 patients with intermediate-risk DTC who were classified into structural incomplete response (SIR), biochemical incomplete response (BIR), indeterminate response (IDR), and excellent response (ER) groups according to the ATA guidelines (version 2015). A downgrade in the classification, such as from initial SIR to final BIR, IDR, or ER, from BIR to IDR or ER, and from initial IDR to final ER, was defined as benefiting from initial 131 I ablation (benefit group). Non-downgraded classification meant non-benefit. RESULTS: 64.78% of patients benefited from the initial 131 I ablation in the final re-evaluation. Gender (OR = 0.038, P  = 0.002), interval time (OR = 0.038, P  = 0.002) and serum ps-Tg (OR = 0.961, P  = 0.001) were independent prognostic factors for benefiting from initial 131 I ablation, with the cutoff value were 5 months and 19.08 ng/ml. CONCLUSION: Patients with intermediate-risk DTC could benefit from initial 131 I ablation. Female patients with intermediate-risk DTC whose interval time <5 months and ps-Tg <19.08 ng/ml were more likely to benefit. Early 131 I ablation for such patients is beneficial for achieving a complete therapeutic response.

Relationship between SUVmax on 18F-FDG PET and PD-L1 expression in liver metastasis lesions after colon radical operation.

PURPOSE: Our study was to investigate the correlation correlation between FDG uptake and PD-L1 expression of liver metastasis in patients with colon cancer, and to determine the value of FDG-PET in predicting PD-L1 expression in liver metastasis of colon cancer. METHODS: A total of 72 patients with confirmed liver metastasis of colon cancer were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of liver metastasis lesions were assessed using 18 F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. RESULTS: PD-L1 expression was significantly correlated with FDG uptake (SUVmax), tumor size, differentiation, survival and cytotoxic T cells infiltration in liver metastasis of colon cancer (P < 0.05). And liver metastases with high counts of infiltrating cytotoxic T cells showed greater FDG uptake than those with low counts of infiltrating cytotoxic T cells. The SUVmax of liver metastases and the degree of differentiation of metastases were closely related to PD-L1 expression, and were independent risk factors.The combined assessment of SUVmax values and tthe degree of differentiation of metastase can help determine PD-L1 expression in liver metastasis of colon cancer. CONCLUSIONS: FDG uptake in liver metastasis of colon cancer was positively correlated with the PD-L1 expression and the number of cytotoxic T cells infiltration. The joint evaluation of two parameters, SUVmax and degree of differentiation, can predict PD-L1 expression in liver metastases.

Relationship between SUVmax on 18F-FDG PET and PD-L1 expression in hepatocellular carcinoma.

PURPOSE: Our study was to investigate the correlation between 18F-FDG uptake in HCC and tumor PD-L1 expression in HCC, and assess the value of 18F-FDG PET/CT imaging for predicting PD-L1 expression in HCC. METHODS: A total of 102 patients with confirmed HCC were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of HCC lesions were assessed using 18F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. RESULTS: The SUVmax of HCC primary tumors was higher in patients with poorly differentiated HCC, large tumor size, portal vein tumor thrombus, lymph node and distant metastases, and death. The SUVmax of HCC are correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. PD-L1 expression was significantly correlated with tumor SUVmax, tumor differentiation, tumor size, portal vein tumor thrombosis, and patient survival status and infiltrating M2 macrophages. Further, our results confirmed that SUVmax, portal vein tumor thrombosis, and the number of infiltrating M2 macrophages were closely related to PD-L1 expression and were independent risk factors by multivariate analysis. The combined assessment of SUVmax values and the presence of portal vein tumor thrombosis by 18F-FDG PET/CT imaging can help determine PD-L1 expression in HCC. CONCLUSIONS: FDG uptake in HCC was positively correlated with the PD-L1 expression and the number of cytotoxic T cells and M2 macrophage infiltration. The combined use of SUVmax and portal vein tumor thrombosis by PET/CT imaging assess the PD-L1 expression better in HCC. These findings also provide a basis for clinical studies to assess the immune status of tumors by PET/CT.

The Value of Stimulated Thyroglobulin Before the First Radioactive Iodine Treatment in Metastasis for Differentiated Thyroid Carcinoma.

BACKGROUND: To evaluate the value of preablative stimulated thyroglobulin (ps-Tg) before the first radioactive ablation iodine (RAI) treatment to predict the postoperative metastasis of DTC. METHODS: A total of 235 DTC patients, who underwent total thyroidectomy and neck lymph node dissection, were enrolled. On the basis of the presence or absence of metastasis, all patients were divided into metastasis (M1) and non-metastasis (M0) groups. Besides, the patients in the M1 group were further divided into two subgroups according to sites of metastasis. These groups included cervical lymph node metastasis and distant metastasis groups. Subsequently, the level of serum ps-Tg was measured 3 - 4 days before the first RAI ablation treatment, whereas 131I whole-body imaging and SPECT/CT tomography were performed 5 - 7 days after radio ablation. Subsequently, the Mann Whitney U test was used to compare the different levels of ps-Tg between the two groups. Additionally, the relationship between ps-Tg and the metastasis of DTC was analyzed through correlation analysis, regression analysis, and the ROC curve. RESULTS: The ps-Tg level in the M1 group was higher than that in the M0 group. Further analysis discovered that the ps-Tg in the distant metastasis group was higher than that in the cervical lymph node metastasis and non-metastasis groups. Also, the ps-Tg level was positively correlated with distant metastasis (r = 0.599, p = 0.000). Besides, the results of multivariate logistic regression analysis outlined that the level of ps-Tg was an independent risk factor for the development of distant metastasis (OR = 1.008, p = 0.018). Subsequently, the results from the ROC analysis also showed a good diagnostic performance for ps-Tg in treating distant metastasis (AUC = 0.964, p = 0.000), and the optimal cutoff value was 61.87 ng/mL. CONCLUSIONS: The ps-Tg in patients with DTC before the first RAI ablation treatment is an independent risk factor and a meaningful indicator in predicting postoperative distant metastasis.

Selective autophagy of intracellular organelles: recent research advances.

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, etc. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, etc. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.

The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses.

Energy deprivation activates the cellular energy sensor AMP-activated protein kinase (AMPK), which in turn induces macroautophagy/autophagy. The mitochondrial-associated ER membrane (MAM) plays a key role in mitochondrial division and autophagy, and the mitochondrial fusion protein MFN2 (mitofusin 2) tethers the MAM, but the mechanism by which AMPK and MFN2 regulate autophagy in response to energy stress remains unclear. Here, we found that energy stress not only triggers mitochondrial fission and autophagy, but more importantly increases the number of MAMs, a process that requires AMPK. Interestingly, under energy stress, considerable amounts of AMPK translocate from cytosol to the MAM and the mitochondrion as mitochondrial fission occurs. Unexpectedly, AMPK interacts directly with MFN2. The autophagic ability of mouse embryonic fibroblasts (MEFs) lacking MFN2 (mfn2-/-) is significantly attenuated in response to energy stress as compared to wild-type MEFs (WT MEFs), while re-expression of MFN2 in mfn2-/- cells rescues the autophagy defects of these cells. The abundance of MAMs is also greatly reduced in MFN2-deficient cells. Functional experiments show that the oxygen consumption rate and the glycolytic function of cells lacking MFN2 but not MFN1 are obviously attenuated, and MFN2 is important for cell survival under energy stress. In conclusion, our study establishes the molecular link between the energy sensor AMPK and the MAM tether MFN2, and reveals the important role of AMPK and MFN2 in energy stress-induced autophagy and MAM dynamics.Abbreviations: ACTB, actin beta; AMPK, AMP-activated protein kinase; BECN1, beclin 1; CANX, calnexin; ER, endoplasmic reticulum; HRP, horseradish peroxidase; EM, electron microscopy; FL, full-length; KD, kinase dead, KO, knockout; MAb, monoclonal antibody; MAMs, mitochondria-associated membranes; MAP1LC3/LC3B, microtubule associated protein 1 light chain 3; MFN2, mitofusin 2; OPA1, OPA1 mitochondrial dynamin like GTPase; PAb, polyclonal antibody; PtdIns3K, class III phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol 3-phosphate; SD, standard deviation; TEM, transmission electron microscopy; TOMM20, translocase of outer mitochondrial membrane 20; ULK1, unc-51 like autophagy activating kinase 1; MEF, mouse embryonic fibroblast; WT, wildtype.

Recent progress in the role of autophagy in neurological diseases.

Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophago-some and then delivered to lysosome for destruction. Recently, tremen-dous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or au-tophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.

Immunofluorescence Staining Protocols for Major Autophagy Proteins Including LC3, P62, and ULK1 in Mammalian Cells in Response to Normoxia and Hypoxia.

Immunofluorescence is an invaluable technique widely used in cell biology. This technique allows visualization of the subcellular distribution of different target proteins or organelles, by specific recognition of the antibody to the endogenous protein itself or to its antigen via the epitope. This technique can be used on tissue sections, cultured cells, or individual cells. Meanwhile, immunofluorescence can also be used in combination with non-antibody fluorescent staining, such as DAPI or fluorescent fusion proteins, e.g., GFP or YFP, etc.Autophagy is a catabolic pathway in which dysfunctional organelles and cellular components are degraded via lysosomes. During this process, cytoplasmic LC3 translocates to autophagosomal membranes. Therefore, cells undergoing autophagy can be identified by visualizing fluorescently labeled LC3 or other autophagy markers. Immunofluorescence is an important part of autophagy detection methods even if observation of the formation of autophagosome by transmission electron microscopy has become a gold standard for characterizing autophagy.By observing the immunofluorescence staining of some key autophagy proteins, we can intuitively evaluate the levels of autophagy in samples. Herein, this protocol describes the predominant method used for the research of autophagy, which mainly focuses on the immunofluorescence staining of cellular LC3, P62, and ULK1 in response to normoxia and hypoxia, by presenting the detailed materials required and methodology.

Gymnemic acid I triggers mechanistic target of rapamycin-mediated ß cells cytoprotection through the promotion of autophagy under high glucose stress.

Gymnemic acid I (GA I) is a bioactive component of Gymnema sylvestre. It is an Indian traditional medicinal herb which has antidiabetic effect. However, the molecular mechanism is remaining to be elucidated. Here, we showed that high glucose promoted the rate of apoptosis, GA I decreased the apoptosis under the high glucose stress. Our further study explored that GA I increased the number of autophagosome and the ratio of light chain 3-I (LC3-I)/LC3-II in MIN-6 cells under the normal or high glucose stress by the methods of western blot analysis and immunofluorescence. It induced autophagy flux and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase ß-1 (p70 S6K/S6K1), which is a substrate of mTOR. GA I decreased the rate of apoptosis and the activity of caspase-3 under the high glucose stress. The inhibition of apoptosis and caspase-3 activity by GA I were increased after treating with autophagy inhibitor in mouse islet ß cells MIN-6. Our data suggested that GA I-induced autophagy protected MIN-6 cells from apoptosis under high glucose stress via inhibition the phosphorylation activity of mTOR.

Organosulfur compounds induce cytoprotective autophagy against apoptosis by inhibiting mTOR phosphorylation activity in macrophages.

Organosulfur compounds (OSCs) are the bioactive components of garlic. Some OSCs have apoptotic or autophagy-inducing effects. Autophagy plays roles in both cytoprotection and apoptosis-related cell death, and the interaction between autophagy and apoptosis is important in the modulation of immune responses. The mechanism of an OSC-mediated effect via the interaction of autophagy and apoptosis is unknown. In this study, the effects of five OSC compounds on autophagy in the macrophage cell line RAW264.7 and primary macrophages were investigated. We found that S-allylcysteine (SAC), diallyl disulde (DADS) and diallyl tetrasulfide (DTS) treatment increased the number of autophagosomes of RAW264.7 cells, inhibited the phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K/S6K1) which is a substrate of mammalian target of rapamycin (mTOR), and significantly enhanced autophagy flux. The induction of autophagy by SAC, DADS and DTS was inhibited by stably knocking down the expression of autophagy-related gene 5 (ATG5) with short hairpin RNA (shRNA). Further experiments confirmed that SAC, DADS and DTS also induced apoptosis in RAW264.7 cells. The induction of apoptosis and Caspase 3 activity by SAC, DADS and DTS were increased by stably knocking down of ATG5 expression with shRNA in RAW264.7 cells or treating with 5 mM 3-MA in primary macrophages. Our results suggest that SAC, DADS and DTS induce both autophagy and apoptosis. The autophagy induction protects macrophages from apoptosis by inhibiting mTOR phosphorylation activity to maintain the mass of immune cells.

PKM2 functions as a potential oncogene and is a crucial target of miR-148a and miR-326 in thyroid tumorigenesis.

In this study, we investigated the biological function of pyruvate kinase M2 (PKM2) and its regulation by deregulated microRNAs (miRNAs) in thyroid cancer (TC). The mRNA and protein expression of PKM2 was examined by quantitative reverse transcription PCR and western blot. The biological role of PKM2 was demonstrated through small interfering RNA-mediated knockdown experiments. The regulation of PKM2 by miR-148a and miR-326 was confirmed by western blot, dual luciferase activity assays, and rescue experiments. PKM2 was overexpressed in TC tissues and cell lines. The knockdown of PKM2 in TC cells suppressed cell proliferation, reduced colony formation, and inhibited cell invasion and migration significantly. Luciferase reporter assays revealed that PKM2 is a direct target of two tumor-suppressive miRNAs, miR-148a and miR-326. Re-expressed PKM2 rescued the anticancer effects of miR-148a. Taken together, these data strongly suggest that, apart from gene amplification and mutation, the activation of PKM2 in TC is partly due to the down-regulation of the tumor-suppressive miRNAs miR-148a and miR-326. Thus, PKM2 is overexpressed and plays an oncogenic role in thyroid carcinogenesis.

Xiaokeping-induced autophagy protects pancreatic ß-cells against apoptosis under high glucose stress.

Xiaokeping (XKP), a prescribed Traditional Chinese Medicine (TCM), has been used to treat patients with type Ⅱ diabetes mellitus for many years; however, the molecular mechanism of its effects is unknown. As the only insulin producer, the pancreatic ß cell plays an important role in diabetes. Whether XKP influences the viability of pancreatic ß cells remains to be substantiated. In the present study, autophagy/apoptosis analyses were used to evaluate the therapeutic effect of XKP on pancreatic ß-cells induced by high glucose levels and to investigate a potential causal molecular mechanism of XKP effect on the cells. The pancreatic ß-cell lines MIN-6 were divided into four groups: control, high glucose (33.3 mmol/L), high glucose with XKP, high glucose with XKP and 3-Methyladenine (3-MA). Immunofluorescence assay was employed to determine autophagosome formation and flow cytometry was used to determine apoptotic rates of the ß cells by the detecting expression of autophagy- and apoptosis-related proteins. High glucose increased the apoptotic rate of ß-cells from 5.37% to 23.24%; however addition of XKP mitigated the rate at 10.92%. Data indicate that autophagy of ß-cells was induced by XKP via the mammalian target of rapamycin (mTOR) pathway. Where the autophagy inhibitor 3-MA was added, the apoptotic rate was 23.94%, similar to the high glucose group rate. The results suggest a potential cytoprotective effect of XKP from high glucose toxicity by its induction of autophagy which may be linked to mTOR-mediated autophagy.

The mitochondrial genome of the lepidopteran host cadaver (Thitarodes sp.) of Ophiocordyceps sinensis and related phylogenetic analysis.

To understand the phylogeny of the host insect (Thitarodes sp.) of the fungus Ophiocordyceps sinensis, we sequenced, annotated and characterized the complete mitochondrial (mt) genome of the host cadaver of a natural O. sinensis. Further, we compared the Thitarodes sp. mt genome with those of the other 7 sequenced Hepialidae and examined the phylogenetic relationships using a constructed Maximum Likelihood (ML) phylogenetic tree and mt genomic features (genetic distances and intergenic spacers). The mt genome is a circular molecule of 16,280bp in length with a high A+T content (81.20%) and contains 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and an AT-rich region. The gene arrangement is identical to the ancestral arrangement but differs from those of other lepidopteran mt genomes because of the arrangement of tRNA genes. The tRNA region, which is located between the AT-rich region and nad2, is trnI/trnQ/trnM (IQM) in Thitarodes sp., rather than the trnM/trnI/trnQ (MIQ) of the Lepidoptera-specific rearrangement. All PCGs begin with the canonical start codons ATN or NTG, except for cox1, which starts with CGA. Most PCGs terminate with the typical stop codon TAA, although some have an incomplete stop codon (T). The 1473bp AT-rich region is located between the rrnS (12S rRNA) and trnI, which is the longest sequenced in a Thitarodes mt genome to date, containing nine 112bp copies and one partial copy of a 55bp sequence. The results derived from the phylogenetic tree, the genetic distances and the intergenic spacers of the mt genome show that the host insect of O. sinensis belongs to the Thitarodes, while Endoclita signifer and Napialus hunanensis form a relatively distinct lineage from Thitarodes. The sequence and full annotation of this moth mt genome will provide more molecular information about the Exoporia within the Lepidoptera, and the clarification of its phylogeny will improve the management of this insect resource and the conservation and sustainable use of this endangered medicinal species in China.

Hydraulic fracture extending into network in shale: reviewing influence factors and their mechanism.

Hydraulic fracture in shale reservoir presents complex network propagation, which has essential difference with traditional plane biwing fracture at forming mechanism. Based on the research results of experiments, field fracturing practice, theory analysis, and numerical simulation, the influence factors and their mechanism of hydraulic fracture extending into network in shale have been systematically analyzed and discussed. Research results show that the fracture propagation in shale reservoir is influenced by the geological and the engineering factors, which includes rock mineral composition, rock mechanical properties, horizontal stress field, natural fractures, treating net pressure, fracturing fluid viscosity, and fracturing scale. This study has important theoretical value and practical significance to understand fracture network propagation mechanism in shale reservoir and contributes to improving the science and efficiency of shale reservoir fracturing design.

Overexpression of SMAR1 Enhances Radiosensitivity in Human Breast Cancer Cell Line MCF7 via Activation of p53 Signaling Pathway.

This study sought to investigate the effect of overexpression of SMAR1 (scaffold/matrix-associated region-binding protein 1) on cell radiosensitivity in breast cancer, as well as elucidate its regulatory mechanism. We constructed a lentiviral expression system to successfully overexpress SMAR1 in human breast cancer cell line MCF7. In addition, overexpression of SMAR1 in MCF7 cells enhanced the radiosensitivity to (89)SrCl2. Moreover, overexpression of SMAR1 significantly induced cell apoptosis rate and G2/M phase arrest under the irradiation of (89)SrCl2. In addition, Western blot analysis showed that overexpression of SMAR1 in MCF cells significantly increased the expression levels of pP53 (ser15), pP53 (ser20), acP53, and p21 and obviously decreased the expression of MDM2 under the irradiation of (89)SrCl2. Notably, these expression changes could be neutralized by PFTα, an inhibitor of p53 signaling pathway that could inhibit p53-dependent transactivation of p53-responsive genes. Therefore, overexpression of SMAR1 may increase radiosensitivity to (89)SrCl2 in breast cancer cell line MCF7 by p53-dependent G2/M checkpoint arrest and apoptosis. Enhanced expression of SMAR1 in tumors will help to improve the clinical efficiency of radiation therapy.