Combination therapy of metformin and atorvastatin against benzopyrene-induced lung cancer via inflammatory signaling pathway.

The most prevalent cause of lung cancer is smoking tobacco, but exposure to second hand smoke, air pollution, and certain chemicals and substances at work can also raise the risk of disease. In this study, we scrutinized the chemoprotective effect of the metformin and atorvastatin combination against benzo[a]pyrene (BaP)-induced lung cancer in mice of Swiss albino. BaP (50 mg/kg) was used for induction of lung cancer and mice were treated with metformin, atorvastatin or their combination. Metformin + atorvastatin combination significantly (p< 0.001) improved the body weight, liver weight, suppressed the lung weight and tumor incidence and altered the levels of immunocompetent cells, polyamines, lung tumor markers, lung parameters and antioxidant parameters, respectively. Metformin + atorvastatin combination also suppressed cytokines levels, inflammatory parameters and caspase parameters. On the basis of the results, we can conclude that metformin + atorvastatin combination remarkably suppressed lung cancer via the inflammatory pathway.

Integrin ß4 Regulates Cell Migration of Lung Adenocarcinoma Through FAK Signaling.

The role of the integrin family in malignancy has received increasing attention. Many studies have confirmed that ITGB4 could activate multiple signal pathways and promote cell migration in various cancers. However, the regulatory role of integrin ß4 (ITGB4) in lung adenocarcinoma (LUAD) is still unclear. Examination of the expression or survival analysis of ITGB4 in cells, pathological samples, and bioinformatics lung adenocarcinoma databases showed ITGB4 was highly expressed in LUAD and significantly associated with poor prognosis. Small interfering RNA and plasmids were performed to investigate the effect of changes in ITGB4 expression on lung adenocarcinoma. Focal adhesion kinase (FAK) inhibitor defactinib was used to further explore the molecular mechanism of ITGB4. The results showed depletion of ITGB4 inhibited migration and activation of FAK signaling pathways in lung adenocarcinoma cells. Moreover, increased ITGB4 expression activated FAK signaling and promoted cell migration, which can be reversed by defactinib. In addition, ITGB4 could interact with FAK in lung adenocarcinoma cells. ITGB4 may promote cell migration of lung adenocarcinoma through FAK signaling pathway and has the potential to be a biomarker for lung adenocarcinoma.

AHNAKs roles in physiology and malignant tumors.

The AHNAK family currently consists of two members, namely AHNAK and AHNAK2, both of which have a molecular weight exceeding 600 kDa. Homologous sequences account for approximately 90% of their composition, indicating a certain degree of similarity in terms of molecular structure and biological functions. AHNAK family members are involved in the regulation of various biological functions, such as calcium channel modulation and membrane repair. Furthermore, with advancements in biological and bioinformatics technologies, research on the relationship between the AHNAK family and tumors has rapidly increased in recent years, and its regulatory role in tumor progression has gradually been discovered. This article briefly describes the physiological functions of the AHNAK family, and reviews and analyzes the expression and molecular regulatory mechanisms of the AHNAK family in malignant tumors using Pubmed and TCGA databases. In summary, AHNAK participates in various physiological and pathological processes in the human body. In multiple types of cancers, abnormal expression of AHNAK and AHNAK2 is associated with prognosis, and they play a key regulatory role in tumor progression by activating signaling pathways such as ERK, MAPK, Wnt, and MEK, as well as promoting epithelial-mesenchymal transition.

FOXM1 and CENPF are associated with a poor prognosis through promoting proliferation and migration in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a clinically challenging disease due to its poor prognosis and limited therapeutic methods. The aim of the present study was to identify prognosis-related genes and therapeutic targets for LUAD. Raw data from the GSE32863, GSE41271 and GSE42127 datasets were downloaded from the Gene Expression Omnibus database. Following normalization, the data were merged into a matrix, which was first used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and survival analysis were performed to screen potential prognosis-related genes. Gene overlaps among DEGs, survival-related genes and WGCNA genes were finally constructed to obtain candidate genes. An analysis with the STRING database was performed to construct a protein-protein interaction network and hub genes were selected using Cytoscape. The candidate genes were finally identified by univariate and multivariate Cox regression analysis. Furthermore, in vivo and in vitro experiments, including immunohistochemistry, immunofluorescence, Cell Counting Kit-8, colony-formation and migration assays, were performed to validate the potential mechanism of these genes in LUAD. Two genes, namely forkhead box M1 (FOXM1) and centromere protein F (CENPF), were identified as unfavorable indicators of prognosis in patients with LUAD. High expression of FOXM1 and CENPF were associated with poor survival. Furthermore, LUAD cells with FOXM1 and CENPF knockdown showed a significant reduction in proliferation and migration (P<0.05). FOXM1 and CENPF may have an essential role in the prognosis of patients with LUAD by influencing cell proliferation and migration, and they provide potential molecular targets for LUAD therapy.

Association between serum HE4 and poor periodontal health in adult women.

OBJECTIVES: The aim of this study is to explore the association between serum human epididymal protein (HE4) levels and poor periodontal health. MATERIALS AND METHODS: Data used in our study from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and Gene Expression Omnibus database (GSE10334 and GSE16134). Periodontitis category was defined by the 2017 classification scheme based on clinical periodontal parameters. Univariate and multivariate logistic regression analyses were used to explore the relationship between serum HE4 levels and the risk of periodontitis. GSEA analysis was performed to investigate the function of HE4. RESULTS: A total of 1715 adult women over the age of 30 were included in our study. Compared with the lowest tertile, individuals in the highest tertile of HE4 levels were more likely to be Stage III/IV periodontitis (ORtertile3vs1 = 2.35, 95% CI: 1.35-4.21). The association was still significant in populations who were less than 60 years old, non-Hispanic white, high school graduate, 1.3 < PI ≤ 3.5, non-smoker, current smoker, non-obese, obese, and who had not diabetes mellitus or had not hypertension. In addition, HE4 expression was upregulated in diseased gingival tissues and involved in cell proliferation and immunity. CONCLUSIONS: Serum HE4 is positively associated with poor periodontal health in adult women. CLINICAL RELEVANCE: Patients with high serum HE4 levels are more likely to have Stage III/IV periodontitis. HE4 has the potential to be used as a biomarker to predict the severity of periodontitis.

A Signature Constructed Based on the Integrin Family Predicts Prognosis and Correlates with the Tumor Microenvironment of Patients with Lung Adenocarcinoma.

As an important element in regulating the tumor microenvironment (TME), integrin plays a key role in tumor progression. This study aimed to establish prognostic signatures to predict the overall survival and identify the immune landscape of patients with lung adenocarcinoma based on integrins. The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus datasets were used to obtain information on mRNA levels and clinical factors (GSE72094). The least absolute shrinkage and selection operator (LASSO) model was used to create a prediction model that included six integrin genes. The nomogram, risk score, and time-dependent receiver operating characteristic analysis all revealed that the signatures had a good prognostic value. The gene signatures may be linked to carcinogenesis and TME, according to a gene set enrichment analysis. The immunological and stromal scores were computed using the ESTIMATE algorithm, and the data revealed, the low-risk group had a higher score. We discovered that the B lymphocytes, plasma, CD4+ T, dendritic, and mast cells were much higher in the group with low-risk using the CiberSort. Inflammatory processes and several HLA family genes were upregulated in the low-risk group. The low-risk group with a better prognosis is more sensitive to immune checkpoint inhibitor medication, according to immunophenoscore (IPS) research. We found that the patients in the high-risk group were more susceptible to chemotherapy than other group patients, according to the prophetic algorithm. The gene signatures could accurately predict the prognosis, identify the immune status of patients with lung adenocarcinoma, and provide guidance for therapy.

Acupuncture for Patients With Chronic Tension-Type Headache: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks. METHODS: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)-defined as a type of sham control by avoiding deqi sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs). RESULTS: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and it was 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group. CONCLUSION: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment. TRIAL: Registration Information: ClinicalTrials.gov: NCT03133884 (https://clinicaltrials.gov/ct2/show/NCT03133884) CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces mean headache days (per month) in patients with chronic tension-type headache.

AHNAK2 Is Associated with Poor Prognosis and Cell Migration in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), as the main subtype of lung cancer, is one of the common causes of cancer-related deaths worldwide. The AHNAK family is correlated with cell structure and migration, cardiac calcium channel signaling, and tumor metastasis. Previous studies showed AHNAK2 could promote tumor progression and cell migration in melanoma and renal clear cell carcinoma. However, the role of AHNAK2 in LUAD remains unknown. METHODS: We examined the levels of AHNAK2 in pathological specimens and the database of Clinical Proteomic Tumor Analysis Consortium-Lung adenocarcinoma (CPTAC-LUAD), The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), Gene Expression Omnibus dataset (GSE72094, GSE26939), and The Genotype-Tissue Expression (GTEx) of lung tissue samples. Univariate Cox regression, multivariate Cox regression, and Kaplan-Meier survival analysis were performed to reveal the relationship between AHNAK2 and prognosis. A nomogram was constructed to predict 2- or 3-year overall survival and validated via calibration curves, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the functional role of AHNAK2 in lung adenocarcinoma. Finally, by transfecting siRNA, we examined the regulatory effect of AHNAK2 on cell migration. RESULTS: The expression of AHNAK2 was upregulated in tumor samples and correlated with poor prognosis in LUAD patients. Nomogram with AHNAK2 and clinical parameters showed a good prediction in overall survival (OS), especially the 2-year OS. In addition, functional analyses and wound healing assay suggested that AHNAK2 might be involved in the regulation of migration in LUAD. CONCLUSION: In summary, our study showed that AHNAK2 might be a novel biomarker in LUAD and revealed the potential mechanism of AHNAK2 in LUAD progression which could provide new insights for target therapy.

Identification Six Metabolic Genes as Potential Biomarkers for Lung Adenocarcinoma.

Metabolic genes have been reported to act as crucial roles in tumor progression. Lung adenocarcinoma (LUAD) is one of the most common cancers worldwide. This study aimed to predict the potential mechanism and novel markers of metabolic signature in LUAD. The gene expression profiles and the clinical parameters were obtained from The Cancer Genome Atlas-Lung adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus data set (GSE72094). A total of 105 differentially expressed metabolic genes of intersect expression in TCGA-LUAD and GSE72094 were screened by R language. Univariate Cox regression model found 18 survival-related genes and then the least absolute shrinkage and selection operator model was successfully constructed. Six significant genes prognostic model was validated though independent prognosis analysis. The model revealed high values for prognostic biomarkers by time-dependent receiver operating characteristic (ROC) analysis, risk score, Heatmap, and nomogram. In addition, Gene Set Enrichment Analysis showed that multiplex metabolism pathways correlated with LUAD. Furthermore, we found the six genes aberrantly expressed in LUAD samples. Our study showed that metabolism pathways play important roles in LUAD progression. The six metabolic genes could predict potential prognostic and diagnostic biomarkers in LUAD.

Information Propagation Formalized Representation of Micro-blog Network Based on Petri Nets.

The description of user behavior in social networks is an important issue for studying social networks. Given that Petri nets can describe the resource flow problem, this study utilizes the features of Petri nets to portray the user behavior states during the message propagation of a micro-blog network and presents an information propagation formalized representation method of a micro-blog network. On this basis, this study analyzed the proposed formalized representation method in detail. We provide examples of applying formalized representation (e.g., micro-blog network addiction of users, user behavior influence, and public opinion analysis). In addition, we introduce the algorithms of formalized representation. We conduct experiments using Sina micro-blog data. Results show that the information propagation formalized representation method of micro-blog network based on Petri nets can depict user behaviors of micro-blog network intuitively and accurately. This study reveals a new perspective for information transmission of a micro-blog network and provides some tools to support public opinion monitoring and micro-blog marketing applications.

Comprehensive analysis of lncRNA-associated competing endogenous RNA network in tongue squamous cell carcinoma.

BACKGROUND: Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) play an important role in the competitive endogenous RNA (ceRNA) networks in that they regulate protein-coding gene expression by sponging microRNAs (miRNAs). However, the understanding of the ceRNA network in tongue squamous cell carcinoma (TSCC) remains limited. METHODS: Expression profile data regarding mRNAs, miRNAs and lncRNAs as well as clinical information on 122 TSCC tissues and 15 normal controls from The Cancer Genome Atlas (TCGA) database were collected. We used the edgR package to identify differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) between TSCC samples and normal samples. In order to explore the functions of DEmRNAs, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed. Subsequently, a ceRNA network was established based on the identified DElncRNAs-DEmiRNAs and DEmiRNAs-DEmRNAs interactions. The RNAs within the ceRNA network were analyzed for their correlation with overall disease survival. Finally, lncRNAs were specifically analyzed for their correlation with clinical features in the included TSCC patient samples. RESULTS: A total of 1867 mRNAs, 828 lncRNAs and 81 miRNAs were identified as differentially expressed in TSCC tissues (-log 2fold change- ≥ 2; adjusted P value <0.01). The resulting ceRNA network included 16 mRNAs, 56 lncRNAs and 6 miRNAs. Ten out of the 56 lncRNAs were found to be associated with the overall survival in TSCC patients (P < 0.05); 10 lncRNAs were correlated with TSCC progression (P < 0.05). CONCLUSION: Our study deepens the understanding of ceRNA network regulatory mechanisms in TSCC. Furthermore, we identified ten lncRNAs (PART1, LINC00261, AL163952.1, C2orf48, FAM87A, LINC00052, LINC00472, STEAP3-AS1, TSPEAR-AS1 and ERVH48-1) as novel, potential prognostic biomarkers and therapeutic targets for TSCC.

Cycle Based Network Centrality.

Paths and cycles are the two pivotal elements in a network. Here, we demonstrate that paths, particularly the shortest ones, are incomplete in information network. However, based on such paths, many network centrality measures are designed. While extensive explorations on paths have been made, modest studies focus on the cycles on measuring network centrality. We study the relationship between the shortest cycle and the shortest path from extensive real-world networks. The results illustrate the incompleteness of the shortest paths on measuring network centrality. Noticing that the shortest cycle is much more robust than the shortest path, we propose two novel cycle-based network centrality measures to address the incompleteness of paths: the shortest cycle closeness centrality (SCC) and the all cycle betweenness centrality (ACC). Notwithstanding we focus on the network centrality problem, our findings on cycles can be applied to explain the incompleteness of paths in applications and could improve the applicability into more scenarios where the paths are employed in network science.

α7nAChR-mediated recruitment of PP1γ promotes TRAF6/NF-κB cascade to facilitate the progression of Hepatocellular Carcinoma.

The cholinergic signaling pathways have been recently implicated in the development of various human cancers. However, the underlying molecular mechanism remains largely unclear. In the present study, we reported that α7 nicotinic acetylcholine receptor (α7nAChR), an important member of nicotinic acetylcholine receptors, interacts with Protein Phosphatase-1γ (PP1γ) in human Hepatocellular Carcinoma (HCC) tissues. In addition, we found that α7nAChR facilitates the ubiquitination and activation of TRAF6 in a PP1γ-dependent manner in HCC cells. Furthermore, we showed that ligand-bounded α7nAChR induces the degradation of IκBα, leading to resultant phosphorylation and nuclear accumulation of NF-κB p65. Accordingly, acetylcholine triggers the expression of critical NF-κB target genes, such as Cyclin D1 and PCNA, as well as the proliferation of HCC cells in a PP1γ- and α7nAChR-dependent manner. Furthermore, we revealed that nicotine-triggered α7nAChR activation promotes oncosphere formation and in vivo tumor growth of HCC cells. Moreover, we showed that the protein levels of both α7nAChR and PP1γ are significantly upregulated in human HCC specimens compared with adjacent non-cancerous ones, and that upregulated expression of the two proteins predict significantly worsened prognosis in HCC patients. These findings together indicate that the cholinergic receptor α7nAChR exerts a facilitating role in HCC development through PP1γ-dependent TRAF6/NF-κB signaling.

Low expression of NKD2 is associated with enhanced cell proliferation and poor prognosis in human hepatocellular carcinoma.

NKD2 is a member of the Naked cuticle (Nkd) protein family and functions as a negative regulator of the Wnt signaling pathway. We investigated the prognostic value of NKD2 expression in hepatocellular carcinoma (HCC). Western blot and immunohistochemical analyses revealed that NKD2 was significantly downregulated in HCC specimens compared with adjacent nontumorous tissues. Next, we found that NKD2 expression correlated significantly with several clinicopathologic features, such as tumor grade, tumor size, and Ki-67 expression. Univariate and multivariate analyses demonstrated that NKD2 was an independent prognostic factor for the survival of HCC patients. In particular, Kaplan-Meier survival curves suggested that low NKD2 was statistically associated with poor overall survival. Furthermore, serum refeeding of cultured HCC cells led to impaired amounts of NKD2 and induced HepG2 and Huh7 cells to transition from the G1 to the S phase. Small interfering RNA-mediated depletion of NKD2 in LO2 hepatocytes caused accelerated cell growth. To further clarify the role of NKD2 in cell cycle progression, a Flag-tagged NKD2 construct was used to overexpress NKD2 exogenously in Huh7 cells. These results showed that overexpression of NKD2 induced G1-phase cell cycle arrest. Reduced expression of NKD2 correlated with hyperactivation of the Wnt/ß-catenin pathway and doxorubicin resistance in HCC cells. On the basis of these findings, we conclude that NKD2 may be a novel prognostic marker and therapeutic target in HCC.

[Deqi(qi arrival) theory in ancient TCM books].

Acupuncturists in all ages emphasize deqi(qi arrival). We arranged and analyzed contents on deqi and qi arrival electronic texts in 1156 ancient medical books through Chinese Medical Code, the major electronic series of books on TCM, with medical classics as well as acupuncture-moxibustion and tuina parts as the emphasis. It is found that deqi is a standard for traditional acupuncture effect evaluation. Meanwhile, it acts on regulating body cold, heat, insufficiency and excess, guiding reinforce-reducing manipulation, determining needle depth, retaining and withdrawing, as well as prognosis, etc. Deqi takes the priority in clinical and scientific research.

The long-term effect of acupuncture for patients with chronic tension-type headache: study protocol for a randomized controlled trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture. DESIGN: A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period. DISCUSSION: Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period. TRIAL REGISTRATION: ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017.

CD109 Mediates Cell Survival in Hepatocellular Carcinoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 75-80 % of primary liver cancer, and usually arises after years of liver disease. Thus it is important to understand the molecular mechanisms which drive or mediate the development of HCC. AIM: In this work, we examined whether CD109 was associated with a poor prognosis in HCC and explored possible underlying mechanisms. METHODS: We examined the CD109 and Ki67 expression levels in 97 patients with HCC using immunohistochemistry. CD109 levels in HCC cells were down-regulated by shRNA transfection. The cycle progression and cell proliferation status of HCC cells were evaluated by flow cytometry and CCK-8 assay. The effect of CD109 on proliferation and apoptosis was investigated by western blot and TUNEL activity assays. RESULTS: The CD109 protein was up-regulated in HCC tissue compared with adjacent noncancerous tissue. CD109 expression levels in the 97 patients with HCC were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that CD109 was a significant predictor of overall survival among HCC patients. CD109 shRNA knockdown delayed the G1-S phase transition, abrogated cell proliferation, and increased cell apoptosis. Furthermore, CD109 impaired TGF-ß/Smad signaling through control of p-smad2. CONCLUSIONS: CD109 promoted HCC proliferation and predicted poor prognosis. In addition, CD109 expression was associated with anti-apoptosis in HCC cells.

Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma.

p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC.