LncRNA SNHG1 Accelerates Cell Proliferation, Migration, and Invasion of Hepatoblastoma Through Mediating miR-6838-5p/PIM3/RhoA Axis.

Hepatoblastoma (HB) is a common primary liver malignant tumor in children. Long non-coding RNAs (lncRNAs) are closely engaged in HB progression. The role and regulatory molecule mechanism of lncRNA small nucleolar RNA host gene 1 (SNHG1) in HB remain unclear. Through qRT-PCR or western blot, we found that SNHG1 and proviral integration site for moloney murine leukemia virus 3 (PIM3) were elevated but miR-6838-5p was decreased in HB cells. Cell biology experiments revealed that SNHG1 depletion or miR-6838-5p upregulation suppressed cell proliferation, migration, and invasion of HB cells. Mechanistically, luciferase activity assay validated that miR-6838-5p could interact with SNHG1 or PIM3. SNHG1 up-regulated PIM3 expression via sponging miR-6838-5p. Moreover, miR-6838-5p inhibitor abolished SNHG1 depletion-mediated suppression of malignant behaviors in HB cells. PIM3 overexpression neutralized miR-6838-5p mimics-mediated repression of malignant phenotypes in HB cells. Furthermore, miR-6838-5p overexpression suppressed RhoA activation, which was restored by PIM3 upregulation. What's more, the results at the cellular level were further verified by nude mice tumor formation experiment. In conclusion, SNHG1 regulated miR-6838-5p/PIM3/RhoA axis to promote malignant phenotypes of HB, which might provide novel therapeutic target for HB treatment.

The progress of PET/MRI in clinical management of patients with pancreatic malignant lesions.

Recently, the morbidity and mortality of pancreatic cancer have been increasing year by year. Because of its deep anatomical location and because most presented patients often suffer from abdominal pain or jaundice, it is difficult to diagnose pancreatic cancer at an early stage, leading to late clinical stage and poor prognosis. integrated positron emission tomography/magnetic resonance imaging (PET/MRI) fusion imaging not only has the characteristics of high resolution and multi-parameter imaging of MRI, but also combines the high sensitivity and the semi-quantitative characteristics of PET. In addition, the continuous development of novel MRI imaging and PET imaging biomarkers provide a unique and precise research direction for future pancreatic cancer research. This review summarizes the value of PET/MRI in the diagnosis, staging, efficacy monitoring, and prognosis evaluation of pancreatic cancer, and prognosis for developing emerging imaging agents and artificial intelligence radiomics in pancreatic cancer.

Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) can be encapsulated into exosomes to participate in intercellular communication, affecting the malignant progression of a variety of tumors. Dysfunction of CD8 + T cells is the main factor in immune escape from hepatocellular carcinoma (HCC). Nevertheless, the effect of exosome-derived circRNAs on CD8 + T-cell dysfunction needs further exploration. METHODS: The effect of circCCAR1 on the tumorigenesis and metastasis of HCC was assessed by in vitro and in vivo functional experiments. The function of circCCAR1 in CD8 + T-cell dysfunction was measured by enzyme-linked immunosorbent assay (ELISA), western blotting and flow cytometry. Chromatin immunoprecipitation, biotinylated RNA pull-down, RNA immunoprecipitation, and MS2 pull-down assays were used to the exploration of mechanism. A mouse model with reconstituted human immune system components (huNSG mice) was constructed to explore the role of exosomal circCCAR1 in the resistance to anti-PD1 therapy in HCC. RESULTS: Increased circCCAR1 levels existed in tumor tissues and exosomes in the plasma of HCC patients, in the culture supernatant and HCC cells. CircCCAR1 accelerated the growth and metastasis of HCC in vitro and in vivo. E1A binding protein p300 (EP300) and eukaryotic translation initiation factor 4A3 (EIF4A3) promoted the biogenesis of circCCAR1, and Wilms tumor 1-associated protein (WTAP)-mediated m6A modification enhanced circCCAR1 stability by binding insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). CircCCAR1 acted as a sponge for miR-127-5p to upregulate its target WTAP and a feedback loop comprising circCCAR1/miR-127-5p/WTAP axis was formed. CircCCAR1 is secreted by HCC cells in a heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1)-dependent manner. Exosomal circCCAR1 was taken in by CD8 + T cells and caused dysfunction of CD8 + T cells by stabilizing the PD-1 protein. CircCCAR1 promoted resistance to anti-PD1 immunotherapy. Furthermore, increased cell division cycle and apoptosis regulator 1 (CCAR1) induced by EP300 promoted the binding of CCAR1 and ß-catenin protein, which further enhanced the transcription of PD-L1. CONCLUSIONS: The circCCAR1/miR-127-5p/WTAP feedback loop enhances the growth and metastasis of HCC. Exosomal circCCAR1 released by HCC cells contributes to immunosuppression by facilitating CD8 + T-cell dysfunction in HCC. CircCCAR1 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for HCC patients.

Dielectric Relaxation and Dielectric Switching Behaviors in (N,N-Diisopropylethylamine) Tetrachloroantimonate(III).

Dielectric switches have drawn renewed attention to the study of their many potential applications with the adjustable switch temperatures (Ts ). Herein, a novel antimony-based halide semiconductor, (N,N-diisopropylethylamine) tetrachloroantimonate ((DIPEA)SbCl4 , DIPEA+ =N,N-diisopropylethylamine), with dielectric relaxation behavior and dielectric switches has been successfully synthesized. This compound, consisting of coordinated anion S b C l 4 ∞ - ${{\left[{{\rm S}{\rm b}{\rm C}{\rm l}}_{4}\right]}_{\infty }^{-}}$ chains and isolated DIPEA+ cations, undergoes an isostructural order-disorder phase transition and shows a step-like dielectric anomaly, which can function as a frequency-tuned dielectric switch with highly adjustable switch temperature (Ts ). Variable-temperature single-crystal structure analyses and first-principles molecular dynamics simulations give information about the general mechanisms of molecular dynamics. This work enriches the dielectric switch family and proves that hybrid metal halides are promising candidates for switchable physical or chemical properties.

miR­92a represses the viability and migration of nerve cells in Hirschsprung's disease by regulating the KLF4/PI3K/AKT pathway.

Hirschsprung's disease (HSCR) is an intestinal disease caused by defects in neural crest cell migration, proliferation, differentiation, and survival. Many reports have proposed that miRNA dysregulation is related to the occurrence of HSCR. However, the roles and mechanisms of miRNAs have not been thoroughly studied. The levels of miR­92a and KLF4 were examined using qRT­PCR and immunohistochemistry, respectively. Cell viability, migration and apoptosis were evaluated by MTT, Transwell and flow cytometry assays, respectively. A dual­luciferase reporter assay was employed to verify the binding relationship between miR­92a and KLF4. Levels of PI3K/AKT signals were further determined by western blot assay. Herein, elevated expression of miR­92a and reduced expression of KLF4 were found in HSCR tissues, and their expression patterns were negatively correlated. Overexpression of miR­92a inhibited cell viability and migration but enhanced cell apoptosis. However, overexpression of KLF4 had the opposite effects. Mechanistically, KLF4 was a target of miR­92a and it negatively affected biological functions by activating PI3K/AKT signaling. These results proved that miR­92a inhibited the proliferation and metastasis of nerve cells by regulating the KLF4/PI3K/AKT axis.

Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma : Prediction of stage I HCC prognosis.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) has been extensively studied. However, the impact on prognosis of stage I HCC has not been well studied at clincopathological, mutational and transcriptional levels. METHODS: Here we first characterized the influencing factors of prognosis of stage I HCC patients by downloading and analyzing the whole-exome somatic mutation data, messenger ribonucleic acid (mRNA) transcription data, along with demographic and clinical information of 163 stage I HCC patients from the TCGA database. The relationship between the influencing factors and HCC prognosis was studied in detail, and a prediction Nomogram model was established. Figures and tables were plotted using the R software. RESULTS: TP53, CTNNB1, TTN, MUC16 and ALB were the top mutated genes in stage I HCC. A series of co-mutations and mutually exclusive mutations were identified. Twenty-nine genes with significant stratification on prognosis were identified, including highly mutated LRP1B, ARID1A and PTPRQ. Patients with wild type (WT) genes unanimously exhibited significantly better overall survival rate than those with mutants. Patients with the top 10% tumor mutational burden (TMB) exhibited significantly worse prognosis than the rest 90%. Further characterization of transcriptional profile revealed that membrane functions, cell skeleton proteins, ion channels, receptor function and cell cycle were comprehensively altered in stage I HCC. Univariate and multivariate analyses were performed at clinicopathological, mutational and transcriptional levels. The combined analysis revealed sex, race, TMB, neoplasm histologic grade, Child-Pugh grade, MMRN1, OXT and COX6A2 transcription as independent risk factors. These factors were used to establish a Nomogram model to predict the prognosis of individual HCC patients. CONCLUSIONS: The influencing factors of prognosis of stage I HCC have been characterized for the first time at clinicopathological, mutational and transcriptional levels. A Nomogram model has been established to predict the prognosis. Further validation is needed to confirm the effectiveness and reliability of the model.

CIRBP Regulates Pancreatic Cancer Cell Ferroptosis and Growth by Directly Binding to p53.

Pancreatic cancer is one of the most malignant gastrointestinal tumors, and it is of great significance to explore the molecular mechanism of its progression and find new biological therapeutic targets. CIRBP is a cold-induced protein that plays a key role in many physiological and pathological processes, but its role in pancreatic cancer is still unclear. The expression of CIRBP in pancreatic cancer tissues was slightly lower than that in normal tissues, and the high expression of CIRBP was beneficial to survival. At the same time, immunohistochemical detection showed that the expression level of CIRBP in the cytoplasm of cancer tissues was significantly lower than that of adjacent tissues; survival curve analysis showed that pancreatic cancer patients with high nuclear CIRBP expression had a longer overall survival period. RIP results showed that CIRBP antibody significantly enriched p53 RNA, indicating that it could directly bind to p53. Cold treatment of pancreatic cancer cells significantly induced the expression of CIRBP, DPP4, NOX1, and FTH1 and inhibited the expression of p53 and GPX4. Cold induction enhanced the accumulation of Fe2+ in cells, promoted the generation of ROS, and inhibited the expression of GSH-Px. Therefore, cold induction promotes the process of ferroptosis by inducing the expression of CIRBP and then regulating key factors such as p53 and GPX4. In addition, cold induction significantly inhibited the proliferation of pancreatic cancer cells and induced cell apoptosis, but after the addition of ferroptosis inhibitor, cell proliferation and apoptosis did not change significantly. Therefore, CIRBP acts as a tumor suppressor gene in pancreatic cancer and induces ferroptosis through the p53/GPX4 pathway to inhibit cell growth, which may be an important target for the diagnosis and treatment of pancreatic cancer.

lncRNA TUG1 regulates angiogenesis via the miR­204­5p/JAK2/STAT3 axis in hepatoblastoma.

Hepatoblastoma is the most common malignant hepatic tumour type with hypervascularity in early childhood. In recent decades, emerging evidence has proven that long non­coding RNAs (lncRNAs) serve an important oncogenic role in the pathogenesis of hepatoblastoma. However, the underlying mechanism of lncRNA taurine upregulated 1 (TUG1) in the angiogenesis of hepatoblastoma remains unknown. The expression patterns of TUG1 and microRNA (miR)­204­5p were detected in hepatoblastoma tissues and cell lines via reverse transcription­quantitative PCR and were analysed using a Pearson's correlation test. A tube formation assay was performed using human umbilical vein endothelial cells to assess the vasculogenic activity of treated HuH­6 cells. ELISA was used to detect the level of the secretory proangiogenic factor VEGFA in the culture media of HuH­6 cells. A dual luciferase reporter assay was performed to validate the binding relationships of TUG1/miR­204­5p and miR­204­5p/Janus kinase 2 (JAK2). Moreover, western blotting was conducted to measure the protein expression levels of VEGFA, phosphorylated (p)­JAK2, JAK2, p­STAT3 and STAT3. It was identified that TUG1 was upregulated, while miR­204­5p was downregulated in hepatoblastoma tissues and cells. TUG1 knockdown inhibited angiogenesis induced by hepatoblastoma cells. Furthermore, miR­204­5p was identified as a target of TUG1. The results demonstrated that TUG1 attenuated the inhibitory effect of miR­204­5p on the JAK2/STAT3 pathway and promoted angiogenesis in hepatoblastoma cells. In summary, TUG1 was upregulated in hepatoblastoma and suppressed miR­204­5p, thereby activating the downstream signalling pathway of JAK2/STAT3 to facilitate angiogenesis. The present findings will provide novel targets for the treatment of hepatoblastoma.

Transcriptome and DNA methylation analysis reveals molecular mechanisms underlying intrahepatic cholangiocarcinoma progression.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with increasing incidence. It has been suggested that DNA methylation drives cancer development. However, the molecular mechanisms underlying iCCA progression and the roles of DNA methylation still remain elusive. In this study, weighted correlation networks were constructed to identify gene modules and hub genes associated with the tumour stage. We identified 12 gene modules, two of which were significantly positively or negatively related to the tumour stage， respectively. Key hub genes SLC2A1, CDH3 and EFHD2 showed increased expression across the tumour stage and were correlated with poor survival, whereas decrease of FAM171A1, ONECUT1 and PHYHIPL was correlated with better survival. Pathway analysis revealed hedgehog pathway was activated in CDH3 up-regulated tumours, and chromosome separation was elevated in tumours expressing high EFHD2. JAK-STAT pathway was overrepresented in ONECUT1 down-regulated tumours, whereas Rho GTPases-formins signalling was activated in PHYHIPL down-regulated tumours. Finally, significant negative associations between expression of EFHD2, PHYHIPL and promoter DNA methylation were detected, and alterations of DNA methylation were correlated with tumour survival. In summary, we identified key genes and pathways that may participate in progression of iCCA and proposed putative roles of DNA methylation in iCCA.

Chiral Switchable Low-Dimensional Perovskite Ferroelectrics.

Low-dimensional hybrid organic-inorganic perovskites (HOIPs) possess more localized electronic states and narrower conduction and valence bands to promote self-trapping of excitons and stronger exciton emission; therefore, they are widely used as building blocks for various applications in the fields of optoelectronics, photovoltaics, light-emitting diodes, luminescence, fluorescence, and so forth. Despite the past decades of intensive study, the discovered low-dimensional chiral HOIPs are rare as of the 1D chiral HOIP single crystals reported in 2003, as well as the low-dimensional chiral HOIP ferroelectrics are particularly scarce since the first chiral two-dimensional (2D) and/or one-dimensional (1D) HOIP ferroelectrics reported. Herein, two new low-dimensional HOIPs with the same conformational formula [R-MPA]2CdCl4 (R-MPA+ = (R)-(-)-1-methyl-3-phenylpropylamine) were successfully synthetized by means of regulating the stoichiometric proportion of R-MPA and CdCl2 in two ways of 1:1 (1) and 2:1 (2). By combining single-crystal X-ray diffraction, circular dichroism (CD) spectroscopy, differential scanning calorimetry, temperature-dependent dielectric constant, temperature-dependent second-harmonic generation (SHG) effect, polarization-dependent SHG response, and P-E hysteresis loop, we reveal that 1 is a 1D nonchiral molecular ferroelectric and 2 is the first zero-dimensional (0D) chiral ferroelectric with distinct CD signals; meanwhile, 2 exhibits increased properties of high-Tc, large dielectric constant, SHG isotropy, and ferroelectricity than that of 1. These results not only shed light on the high tunability of the low-dimensional HOIP ferroelectrics but also open up an avenue to explore multifunctional chiral ferroelectrics.

High pressure and elastic properties of a guanidinium-formate hybrid perovskite.

The high pressure and elastic properties of a hybrid ABX3-type perovskite, [C(NH2)3][Cd(HCOO)3] (CdGF), based on the A-site guest molecules are revealed via combining the high-pressure synchrotron X-ray diffraction experiments with density functional theory (DFT) calculations. The experimental results indicate that the anisotropic axial compressibilities are Ka = 2.8(4) and Kc = 20.9(10) TPa-1 within the pressure scope of 4.12 GPa, and calculations reveal the microscopic evolution of structure under pressure and demonstrate that this structural anisotropy is a consequence of the directional guest molecule and the cooperative effect of hydrogen bonding and octahedral tilting. In addition, full elastic constants of the perovskite were calculated to describe Young's moduli, shear moduli and Poisson's ratios. Notably, these discrete moduli are governed by the orientational guest molecule suggesting that the perovskite may display positive (negative) linear compression if it is flexible (rigid) along one principal axis.

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis.

OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

miR-125b acts as anti-fibrotic therapeutic target through regulating Gli3 in vivo and in vitro.

INTRODUCTION AND OBJECTIVES: Liver fibrosis is a major characteristic of most chronic liver diseases which leads to accumulation of extracellular matrix (ECM) proteins. Hedgehog (Hh) pathway activated by Gli genes participated in the pathogenesis of liver fibrosis. However, the regulatory role of miR-125b in liver fibrosis via targeting Gli genes remains unknown. MATERIALS AND METHODS: RT-qPCR and western blot were employed to the expression levels of mRNA and protein, respectively. The fibrosis level of liver tissue was determined by Masson's trichrome staining. The interaction between miR-125b and Gli3 was tested by luciferase reporter assay. In addition, LX2 cells were activated and CCl4-induced rat model was used in this study. RESULTS: miR-125b was significantly declined in serum samples of the clinical liver fibrosis patient, activated LX2 cells and the liver tissues of the CCl4-induced rat model. Furthermore, in cellular level, the alpha-smooth muscle actin (α-SMA) and Albumin expressions were ascending and descending in LX2 cells, respectively, with the decline of miR-125b. However, when transfecting with miR-125b mimic, the expressions of α-SMA and Albumin was reversed and Gli3 expression was notably repressed in LX2 cells. The target interaction between miR-125b and Gli3 was determined by dual-luciferase assays. It was further discovered that the changes of α-SMA, Albumin, and Gli3 were similar to the expression trend in LX2 cells with miR-125b mimic transfection. CONCLUSION: These results suggested that miR-125b might be protective against liver fibrosis via regulating Gli3 and it might be a promising target in the development of novel therapies to treat pathological fibrotic disorders.

Light-Induced Bending of Needle-Like Crystals of Naphthylvinylbenzoxazole Triggered by trans-cis Isomerization.

New diarylethene derivatives containing benzoxazole (NBO) and benzothiazole (NBT) have been synthesized. Light-induced trans-cis isomerization of NBO and NBT took place in crystals, and only induced the needle-like crystals of NBO to bend backwards away from the UV light source. The movement of the atoms was deemed to take place during the isomerization of NBO; hence, strain would be produced and accumulated rapidly in the surface of crystals exposed to UV light. The uniform release of strain led to the bending of needle-like crystals. The light-induced trans-cis isomerization efficiency of NBT was too low to drive the motion of crystals, which might have originated from the large repulsion between naphthyl and benzothiazole. These results provide a new platform for the transformation of light energy into mechanical energy in molecular crystals through the unimolecular photochemical reaction of diarylethene derivatives.

Upregulation of NM23-E2 accelerates the liver regeneration after 40% decreased-size liver transplantation in rats.

BACKGROUND: Potential of liver regeneration after living-donor liver transplantation is closely associated with the recipient's prognosis, whereas exogenous gene might regulate the liver regeneration progress. NM23 is a multifunctional gene, which inhibits tumor metastasis and regulates cell proliferation, differentiation, development, and apoptosis; however, there is little research about NM23 in promoting liver cell proliferation. METHODS: To investigate the effect of NM23-E2 on the liver cell proliferation, the NM23-E2 overexpression vector or negative control vector was transfected into BRL-3A cells and donor liver, respectively. NM23-E2, Cyclin D1, and PCNA expression levels in BRL-3A cells and liver tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Cell Counting Kit-8 was used to detect cell proliferation and flow cytometry for investigating cell cycle. The liver regeneration rate was determined by calculating (regenerated-liver weight of recipient - liver weight of donor/liver weight of donor) × 100%. RESULTS: NM23-E2 overexpression increased the NM23-E2, Cyclin D1, and PCNA levels significantly in BRL-3A cells and liver tissues (P < 0.05). The number of S phase cells was more than that of negative control group, and cell proliferation rate was higher than that of the control group in BRL-3A cells markedly (P < 0.05). Moreover, the liver regeneration rate in the NM23-E2 overexpression group was also higher than that in negative control group on postoperative day 1, day 3, day 5, and day 7. CONCLUSIONS: Overexpression of NM23-E2 can increase Cyclin D1 and PCNA expression, shorten cell cycle, and thereby promoting the proliferation of liver cells and accelerating the regeneration of liver after 40% decreased-size rat liver transplantation.

Uniaxial Negative Thermal Expansion and Mechanical Properties of a Zinc-Formate Framework.

The thermal expansion behavior of a metal-formate framework, Zn(HCOO)2·2(H2O) (1), has been systematically studied via variable temperature single-crystal X-ray diffraction. Our results demonstrate that this formate exhibits significant negative thermal expansion (NTE, -26(2) MK-1) along its c-axis. Detailed structural analyses reveal that the large NTE response is attributed to the 'hinge-strut' like framework motion. In addition, the fundamental mechanical properties of framework 1 have been explored via nanoindentation experiments. The measured elastic modulus and hardness properties on the (00-2)/(100)/(110) facets are 35.5/35.0/27.1 and 2.04/1.83/0.47 GPa, respectively. The stiffness and hardness anisotropy can be correlated well with the underlying framework structure, like its thermoelastic behavior.

TMP21 modulates cell growth in papillary thyroid cancer cells by inducing autophagy through activation of the AMPK/mTOR pathway.

OBJECTIVE: To investigate the role of transmembrane protein (TMP) 21 in human thyroid cancer. METHODS: The recombinant expression vector pcDNA3.1 (+)-TMP21 and specific small interfering RNAs (siRNA) against TMP21 were transfected into a papillary thyroid cancer cell line (TPC1). After transfection, the expression of TMP21 was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, cell viability and apoptosis rate were respectively determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry (FCM). Additionally, Western blotting was performed to analyze the adenosine monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways associated protein (P-AMPKα(Thr172), P-mTOR(Ser2448), light chain (LC)-II/LC3-I, and P-S6K(Thr389)) after pre-treatment with AMPK inhibitor, compound C (Com C) and siTMP21. RESULTS: The TMP21 protein level and cell viability were significantly higher, but apoptotic rate was significantly lower by transfection with pcDNA3.1-TMP21 than those in control group (P < 0.05), and reverse results were obtained by transfection with siTMP21. However, qRT-PCR showed different results due to the feedback inhibition of mRNA. Besides, silencing of TMP21 significantly reduced the levels of P-mTOR(Ser2448) and P-S6K(Thr389) (P < 0.05), but significantly increased the levels of P-AMPKα(Thr172) and LC3-II/LC3-I compared with the control group (P < 0.01). Whereas, the levels of P-AMPKα(Thr172) and LC3-II/LC3-I were significantly decreased by Com C compared with the control group (P < 0.05). CONCLUSION: TMP21 modulates cell growth in TPC1 cells by inducing autophagy, which may be associated with activation of AMPK/mTOR pathway.