Retracted: Long noncoding RNA MEG3 is a tumor suppressor in choriocarcinoma by upregulation of microRNA-211

Tumor suppressor long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) exists in various cancers. Nonetheless, the functions of lncRNA MEG3 in choriocarcinoma (CC) are still not well studied. We explored the effects of lncRNA MEG3 on human CC JEG-3 and BeWo cells. lncRNA MEG3 was overexpressed, and the effects of lncRNA MEG3 on cell viability, proliferation, apoptosis, migration, and invasion were assessed by the cell counting kit-8 assay, western blot analysis, flow cytometry (plus western blot analysis), and transwell assay (plus western blot analysis), respectively. Then, the expression level of miR-211 was detected by real-time quantitative polymerase chain reaction. After that, the effects of dysregulated microRNA-211 (miR-211) with overexpressing lncRNA MEG3 on JEG-3 cells and BeWo cells were testified. Western blot analysis was used to study the involvements of the signaling pathways in the lncRNA MEG3-associated modulation. We found that lncRNA MEG3 upregulation reduced cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis. Expression of miR-211 was upregulated after lncRNA MEG3 overexpression. Effects of lncRNA MEG3 overexpression were augmented by miR-211 overexpression, while they were declined by miR-211 silencing. Phosphorylated levels of PI3K, AKT, and AMP-activated protein kinase (AMPK) were decreased by lncRNA MEG3 overexpression via regulation of miR-211. To sum up, lncRNA MEG3 could repress proliferation, migration and invasion, and promote apoptosis of JEG-3 and BeWo cells through upregulating miR-211. The PI3K/AKT and AMPK pathways were inhibited by lncRNA MEG3 overexpression via regulation of miR-211.     

Fractalkine/CX3CR1 induces apoptosis resistance and proliferation through the activation of the AKT/NF‐κB cascade in pancreatic cancer cells

Fractalkine (FKN, CX3CL1) is highly expressed in a majority of malignant solid tumours. Fractalkine is the only known ligand for CX3CR1. In this study, we performed an analysis to determine the effects of fractalkine/CX3CR1 on modulating apoptosis and explored the related mechanisms. The expression of fractalkine/CX3CR1 was detected by immunohistochemistry and western blotting. The levels of AKT/p‐AKT, BCL‐xl, and BCL‐2 were detected by western blotting. Then, the effects of exogenous and endogenous fractalkine on the regulation of tumour apoptosis and proliferation were investigated. The mechanism of fractalkine/CX3CR1 on modulating apoptosis in cancer cells through the activation of AKT/NF‐κB/p65 signals was evaluated. The effect of fractalkine on regulating cell cycle distribution was also tested. Fractalkine, AKT/p‐AKT, and apoptotic regulatory proteins BCL‐xl and BCL‐2 were highly expressed in human pancreatic cancer tissues. In vitro, fractalkine/CX3CR1 promoted proliferation and mediated resistance to apoptosis in pancreatic cancer cells. The antiapoptotic effect of fractalkine was induced by the activation of AKT/NF‐κB/p65 signalling in pancreatic cancer cells. The NF‐κB/p65 contributes to promote the expressions of BCL‐xl and BCL‐2 and reduce caspase activity, thereby inhibiting apoptotic processes. Treatment with fractalkine resulted in the enrichment of pancreatic cancer cells in S phase with a concomitant decrease in the number of cells in G1 phase. The present study demonstrated the function of fractalkine in the activation of the AKT/NF‐κB/p65 signalling cascade and mediation of apoptosis resistance in pancreatic cancer cells. Fractalkine/CX3CR1 could serve as a diagnostic marker and as a potential target for chemotherapy in early stage pancreatic cancer. Pancreatic cancer is characterized by local recurrence, neural invasion, or distant metastasis. The present study demonstrated the overexpression of fractalkine/CX3CR1 in pancreatic cancer tissues, indicating its important role in the tumourigenesis of pancreatic cancer, and suggested that the overexpression of fractalkine/CX3CR1 could serve as a diagnostic marker for pancreatic cancer. Moreover, we reveal the mechanism that fractalkine functions on the activation of the AKT/NF‐κB/p65 signalling cascade and regulation of the antiapoptosis process in pancreatic cancer cells. Fractalkine/CX3CR1 could serve as an effective therapeutic target of chemotherapeutic and biologic agents in early stage pancreatic cancer.     

Down‐regulation of mitogen‐activated protein kinases and nuclear factor‐κB signaling is involved in rapamycin suppression of TLR2‐induced inflammatory response in monocytic THP‐1 cells

Tripalmitoyl‐S‐glycero‐Cys‐(Lys) 4 (Pam3CSK4) interacted with TLR2 induces inflammatory responses through the mitogen‐activated protein kinases (MAPKs) and nuclear factor‐κB (NF‐κB) signal pathway. Rapamycin can suppress TLR‐induced inflammatory responses; however, the detailed molecular mechanism is not fully understood. Here, the mechanism by which rapamycin suppresses TLR2‐induced inflammatory responses was investigated. It was found that Pam3CSK4‐induced pro‐inflammatory cytokines were significantly down‐regulated at both the mRNA and protein levels in THP‐1 cells pre‐treated with various concentrations of rapamycin. Inhibition of phosphatidylinositol 3‐kinase/protein kinase‐B (PI3K/AKT) signaling did not suppress the expression of pro‐inflammatory cytokines, indicating that the immunosuppression mediated by rapamycin in THP1 cells is independent of the PI3K/AKT pathway. RT‐PCR showed that Erk and NF‐κB signal pathways are related to the production of pro‐inflammatory cytokines. Inhibition of Erk or NF‐κB signaling significantly down‐regulated production of pro‐inflammatory cytokines. Additionally, western blot showed that pre‐treatment of THP‐1 cells with rapamycin down‐regulates MAPKs and NF‐κB signaling induced by Pam3CSK4 stimulation, suggesting that rapamycin suppresses Pam3CSK4‐induced pro‐inflammatory cytokines via inhibition of TLR2 signaling. It was concluded that rapamycin suppresses TLR2‐induced inflammatory responses by down‐regulation of Erk and NF‐κB signaling.     

Corilagin suppresses RANKL‐induced osteoclastogenesis and inhibits oestrogen deficiency‐induced bone loss via the NF‐κB and PI3K/AKT signalling pathways

Over‐activated osteoclastogenesis, which is initiated by inflammation, has been implicated in osteoporosis. Corilagin, a natural compound extracted from various medicinal herbaceous plants, such as Cinnamomum cassia, has antioxidant and anti‐inflammatory activities. We found that Corilagin suppressed osteoclast differentiation in a dose‐dependent manner, significantly decreased osteoclast‐related gene expression and impaired bone resorption by osteoclasts. Moreover, phosphorylation of members of the nuclear factor‐kappaB (NF‐κB) and PI3K/AKT signalling pathways was reduced by Corilagin. In a murine model of osteoporosis, Corilagin inhibited osteoclast functions in vivo and restored oestrogen deficiency‐induced bone loss. In conclusion, our findings suggested that Corilagin inhibited osteoclastogenesis by down‐regulating the NF‐κB and PI3K/AKT signalling pathways, thus showing its potential possibility for the treatment of osteoporosis.     

β‐Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav‐1/AKT/NF‐κB Signaling Pathway

β‐carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β‐carotene has an antitumor effect. However, the efficacy of β‐carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β‐carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin‐1 (Cav‐1) protein. Cav‐1 protein was expressed only in ESCC cells, not in Het‐1A cells. Moreover, β‐carotene triggered apoptosis, induced cell cycle G0?G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β‐carotene on the Cav‐1‐mediated AKT/NF‐κB pathway. The results showed that the level of AKT and NF‐κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl‐2 ratio. Correspondingly, the activity of Caspase‐3 was also enhanced. These data suggest that β‐carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells.     

Schisantherin A protects renal tubular epithelial cells from hypoxia/reoxygenation injury through the activation of PI3K/Akt signaling pathway

Schisantherin A (SchA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, was reported to possess anti‐inflammatory and antioxidant activities. However, its protective effect against renal ischemia‐reperfusion (I/R) injury in human renal tubular epithelial cells subjected to hypoxia/reoxygenation (H/R) has never been studied. Thus, herein, we investigated the effect of SchA on renal I/R injury in vitro. Our results demonstrated that SchA pretreatment significantly improved HK‐2 cell viability exposed to H/R. Pretreatment with SchA markedly inhibited the levels of reactive oxygen species and malondialdehyde, as well as suppressed the production of tumor necrosis factor‐α (TNF‐α), interleukin‐1β, and interleukin‐6 in H/R‐stimulated HK‐2 cells. In addition, SchA also suppressed H/R‐induced HK‐2 cell apoptosis. Furthermore, this protective effect of SchA was mediated through the PI3K/Akt signaling pathway in HK‐2 cells. These findings showed that SchA may exert a protective effect on renal tubular epithelial cells against H/R injury through the activation of PI3K/Akt signaling pathway.     

LIGHT/IFN‐γ triggers β cells apoptosis via NF‐κB/Bcl2‐dependent mitochondrial pathway

LIGHT recruits and activates naive T cells in the islets at the onset of diabetes. IFN‐γ secreted by activated T lymphocytes is involved in beta cell apoptosis. However, whether LIGHT sensitizes IFNγ‐induced beta cells destruction remains unclear. In this study, we used the murine beta cell line MIN6 and primary islet cells as models for investigating the underlying cellular mechanisms involved in LIGHT/IFNγ – induced pancreatic beta cell destruction. LIGHT and IFN‐γ synergistically reduced MIN6 and primary islet cells viability; decreased cell viability was due to apoptosis, as demonstrated by a significant increase in Annexin V⁺ cell percentage, detected by flow cytometry. In addition to marked increases in cytochrome c release and NF‐κB activation, the combination of LIGHT and IFN‐γ caused an obvious decrease in expression of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL, but an increase in expression of the pro‐apoptotic proteins Bak and Bax in MIN6 cells. Accordingly, LIGHT deficiency led to a decrease in NF‐κB activation and Bak expression, and peri‐insulitis in non‐obese diabetes mice. Inhibition of NF‐κB activation with the specific NF‐κB inhibitor, PDTC (pyrrolidine dithiocarbamate), reversed Bcl‐xL down‐regulation and Bax up‐regulation, and led to a significant increase in LIGHT‐ and IFN‐γ‐treated cell viability. Moreover, cleaved caspase‐9, ‐3, and PARP (poly (ADP‐ribose) polymerase) were observed after LIGHT and IFN‐γ treatment. Pretreatment with caspase inhibitors remarkably attenuated LIGHT‐ and IFNγ‐induced cell apoptosis. Taken together, our results indicate that LIGHT signalling pathway combined with IFN‐γ induces beta cells apoptosis via an NF‐κB/Bcl2‐dependent mitochondrial pathway.     

Retracted: Long noncoding RNA MEG3 inhibits proliferation and migration but induces autophagy by regulation of Sirt7 and PI3K/AKT/mTOR pathway in glioma cells

Glioma is a common primary brain tumor with high mortality rate and poor prognosis. Long noncoding RNA maternally expressed gene 3 (MEG3) is a tumor suppressor in diverse cancer types. However, the role of MEG3 in glioma remains unclear. We aimed to explore the effects of MEG3 on U251 cells as well as the underlying mechanisms. U251 cells were stably transfected with different recombined plasmids to overexpress or silence MEG3. Effects of aberrantly expressed MEG3 on cell viability, migration, apoptosis, expressions of apoptosis-associated and autophagy-associated proteins, and phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathway were all evaluated. Then, messenger RNA (mRNA) and protein expression of Sirt7 in cells abnormally expressing MEG3 were estimated. In addition, effects of abnormally expressed MEG3 and Sirt7 on U251 cells were determined to reveal the underlying mechanism of MEG3-associated modulation. Cell viability and migration were significantly reduced by MEG3 overexpression whereas cell apoptosis as well as Bax and cleaved caspase-3/-9 proteins were obviously induced. Beclin-1 and LC3-II/LC3-I were upregulated and p62 was downregulated in MEG3 overexpressed cells. In addition, the autophagy pharmacological inhibitor (3-methyladenine, 3-MA) affected the effect of MEG3 overexpression on cell proliferation. Furthermore, the phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathway were all reduced by MEG3 overexpression. Sirt7 was positively regulated by MEG3 expression, and effects of MEG3 overexpression on U251 cells were ameliorated by Sirt7 silence. MEG3 suppressed cell proliferation and migration but promoted autophagy in U251 cells through positively regulating Sirt7, involving in the inhibition of the PI3K/AKT/mTOR pathway.     

Gastrodin relieves inflammation injury induced by lipopolysaccharides in MRC‐5 cells by up‐regulation of miR‐103

The beneficial function of gastrodin towards many inflammatory diseases has been identified. This study designed to see the influence of gastrodin in a cell model of chronic obstructive pulmonary disease (COPD). MRC‐5 cells were treated by LPS, before which gastrodin was administrated. The effects of gastrodin were evaluated by conducting CCK‐8, FITC‐PI double staining, Western blot, qRT‐PCR and ELISA. Besides this, the downstream effector and signalling were studied to decode how gastrodin exerted its function. And dual‐luciferase assay was used to detect the targeting link between miR‐103 and lipoprotein receptor‐related protein 1 (LRP1). LPS induced apoptosis and the release of MCP‐1, IL‐6 and TNF‐α in MRC‐5 cells. Pre‐treating MRC‐5 cells with gastrodin attenuated LPS‐induced cell damage. Meanwhile, p38/JNK and NF‐κB pathways induced by LPS were repressed by gastrodin. miR‐103 expression was elevated by gastrodin. Further, the protective functions of gastrodin were attenuated by miR‐103 silencing. And LRP1 was a target of miR‐103 and negatively regulated by miR‐103. The in vitro data illustrated the protective function of gastrodin in LPS‐injured MRC‐5 cells. Gastrodin exerted its function possibly by up‐regulating miR‐103 and modulating p38/JNK and NF‐κB pathways.     

Retracted: Nimotuzuma restrains proliferation and induces apoptosis in human osteosarcoma cells by regulation of EGFR/PI3K/AKT signal pathway

Osteosarcoma (OS) is a conversant malignant bone tumor, commonly occurs in children and adolescents. Nimotuzuma is an epidermal growth factor receptor (EGRF) monoclonal antibody agent, which has been exploited in varied solid tumors. Nevertheless, the functions of Nimotuzuma in OS remain blurry. We attempted to disclose the impacts of Nimotuzuma on OS cells proliferation and apoptosis. OS MG-63 and U2OS cells were stimulated with the disparate doses of Nimotuzuma. Then, cell viability, cell cycle, and apoptosis were appraised through executing CCK-8 and flow cytometry assays. Moreover, the change of mitochondrial membrane potential (ΔΨm) was estimated via JC-1 fluorescent probe to further probe the impacts of Nimotuzuma on cell apoptosis. The proteins of cell apoptosis, cell cycle, and EGFR/PI3K/AKT were appraised via western blot. Eventually, Nimotuzuma together EGRF or PI3K inhibitor (LY294002) were utilized to dispose MG-63 to further uncover the latent mechanism. We found that Nimotuzuma remarkably repressed cell viability at a time- and dose-dependent manners in MG-63 and U2OS cells. The percentage of the S phase cells was evidently reduced by Nimotuzuma through regulating P21, Cyclin E1, and Cyclin D1. In addition, Nimotuzuma obviously evoked cell apoptosis, meanwhile elevated Bid, Bax, and cleaved-caspase-3. Further exploration showed that Nimotuzuma decreased ΔΨm in a dose-dependent manner in MG-63 and U2OS cells. Besides, we discovered the repressive functions of Nimotuzuma in OS cells proliferation and apoptosis via hindering the EGFR/PI3K/AKT pathway. These investigations testified that Nimotuzuma repressed cell growth by restraining the EGFR/PI3K/AKT pathway in OS cells, hinting the antitumor activity of Nimotuzuma in OS.     

Central dopamine action modulates neuropeptide‐controlled appetite via the hypothalamic PI3K/NF‐κB‐dependent mechanism

Hypothalamic neuropeptides, including neuropeptide Y (NPY) and proopiomelanocortin (POMC), have been found to control the appetite‐suppressing effect of amphetamine (AMPH). In this study, we have examined whether dopamine receptor (DAR), phosphatidylinositol 3‐kinase (PI3K) and nuclear factor‐kappaB (NF‐κB) are involved in AMPH's action. We administered AMPH to rats once a day for 4 days and assessed and compared changes in hypothalamic NPY, melanocortin receptor 4 (MC4R), PI3K, pAkt and NF‐κB expression. We found that the inhibition of DAR increased NPY, but decreased MC4R, PI3K and NF‐κB expression, compared with AMPH‐treated rats. Moreover, MC4R, PI3K, pAkt and NF‐κB increased with the maximum response on Day 2, which was consistent with the response of feeding behavior, but was opposite to the expression of NPY. Furthermore, we found that the intracerebroventricular infusion of the PI3K inhibitor or NF‐κB antisense could attenuate AMPH‐induced anorexia, and partially reverse the expression of NPY, MC4R, PI3K, Akt and NF‐κB back toward a normal level. We, therefore, suggest that DAR–PI3K–NF‐κB signaling in the hypothalamus plays functional roles in the modulation of NPY and POMC neurotransmissions and in the control of AMPH‐evoked appetite suppression.     

CUDC‐907 blocks multiple pro‐survival signals and abrogates microenvironment protection in CLL

CUDC‐907, a dual PI3K/HDAC inhibitor, has been proposed to have therapeutic potential in hematopoietic malignancies. However, the molecular mechanisms of its effects in chronic lymphocytic leukaemia (CLL) remain elusive. We show that CLL cells are sensitive to CUDC‐907, even under conditions similar to the protective microenvironment of proliferation centres. CUDC‐907 inhibited PI3K/AKT and HDAC activity, as expected, but also suppressed RAF/MEK/ERK and STAT3 signalling and reduced the expression of anti‐apoptotic BCL‐2 family proteins BCL‐2, BCL‐xL, and MCL‐1. Moreover, CUDC‐907 downregulated cytokines BAFF and APRIL and their receptors BAFFR, TACI, and BCMA, thus blocking BAFF‐induced NF‐κB signalling. T cell chemokines CCL3/4/17/22 and phosphorylation of CXCR4 were also reduced by CUDC‐907. These data indicated that CUDC‐907 abrogates different protective signals and suggested that it might sensitize CLL cells to other drugs. Indeed, combinations of low concentrations of CUDC‐907 with inhibitors of BCL2, BTK, or the NF‐κB pathway showed a potent synergistic effect. Our data indicate that, apart from its known functions, CUDC‐907 blocks multiple pro‐survival pathways to overcome microenvironment protection in CLL cells. This provides a rationale to evaluate the clinical relevance of CUDC‐907 in combination therapies with other targeted inhibitors.     

Schizandrin protects H9c2 cells against lipopolysaccharide‐induced injury by downregulating Smad3

Schizandrin is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill with antioxidant and anti‐inflammatory properties. The objective of this study was to explore the potential effects of schizandrin on a cell model of myocarditis. The H9c2 cells were treated with schizandrin alone or in combination with lipopolysaccharide (LPS), after which, cell survival, migration, and the release of inflammatory cytokines were assessed. Moreover, downstream effectors and signaling pathways were studied to reveal the possible underlying mechanism. As a result, LPS stimulation induced significant cell damage as cell viability was repressed and the apoptosis was induced. In the meantime, LPS promoted the release of proinflammatory cytokines including interleukin 1β (IL‐1β), IL‐8, IL‐6, and tumor necrosis factor (TNF‐α) while repressing the release of the anti‐inflammatory cytokine IL‐10. Schizandrin could promote H9c2 cell migration and long‐term treatment (7 days) enhanced cell viability. More interestingly, pretreatment with schizandrin attenuated LPS‐induced cell loss and inflammatory response. Besides this, Smad3 was a downstream effector of schizandrin. The beneficial effects of schizandrin on the H9c2 cells were attenuated when Smad3 was overexpressed. Moreover, the silencing of Smad3 deactivated c‐Jun N‐terminal kinase (JNK) and nuclear factor κB (NF‐κB) pathways. This study preliminarily demonstrated that schizandrin prevented LPS‐induced injury in the H9c2 cells and promoted the recovery of myocardial tissues by enhancing cell viability and migration. Schizandrin conferred its beneficial effects possibly by downregulating Smad3 and inhibiting the activation of JNK and NF‐κB pathways.     

miR‐124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast‐like synoviocytes via targeting PIK3/NF‐κB pathway

Abnormal hyperplasia of fibroblast‐like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR‐124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF‐κB in RAFLS was examined by real‐time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)‐α and interleukin (IL)‐6 was detected by ELISA. The joint swelling and inflammation in collagen‐induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR‐124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR‐124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR‐124a inhibited the expression of the key components of the PIK3/Akt/NF‐κB signal pathway and inhibited the expression of pro‐inflammatory factors TNF‐α and IL‐6. Local overexpression of miR‐124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR‐124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF‐κB pathway. miR‐124a is a promising therapeutic target for RA.     

Apoptosis‐inducing effect of garcinol is mediated by NF‐κB signaling in breast cancer cells

Garcinol, obtained from Garcinia indica in tropical regions, is used for its numerous biological effects. Its anti‐cancer activity has been suggested but the mechanism of action has not been studied in‐detail, especially there is no report on its action against breast cancer cells. Here we tested our hypothesis that garcinol may act as an anti‐proliferative and apoptosis‐inducing agent against breast cancer cell lines. Using multiple techniques such as MTT, Histone‐DNA ELISA, Annexin V‐PI staining, Western blot for activated caspases and cleaved PARP, homogenous caspase‐3/7 fluorometric assay and EMSA, we investigated the mechanism of apoptosis‐inducing effect of garcinol in ER‐positive MCF‐7 and ER‐negative MDA‐MB‐231 cells. We found that garcinol exhibits dose‐dependent cancer cell‐specific growth inhibition in both the cell lines with a concomitant induction of apoptosis, and has no effect on non‐tumorigenic MCF‐10A cells. Our results suggested induction of caspase‐mediated apoptosis in highly metastatic MDA‐MB‐231 cells by garcinol. Down‐regulation of NF‐κB signaling pathway was observed to be the mechanism of apoptosis‐induction. Garcinol inhibited constitutive NF‐κB activity, which was consistent with down‐regulation of NF‐κB‐regulated genes. This is the first report on anti‐proliferative and apoptosis‐inducing action of garcinol against human breast cancer cells and the results suggest that this natural compound merits investigation as a potential chemo‐preventive/‐therapeutic agent, especially against breast cancer. J. Cell. Biochem. 109: 1134–1141, 2010. © 2010 Wiley‐Liss, Inc.     

Repression of Kisspeptin1 weakens hydrogen peroxide‐caused injury in HTR8 cells via adjusting PI3K/AKT/mTOR pathway

Kisspeptin1 (KISS1) is a tumor metastatic suppressor, and its increased expression is validated in human placenta trophoblast cells. Nonetheless, the actions of KISS1 in hydrogen peroxide (H₂O₂)‐impaired human trophoblast HTR8 cells still remain imprecise. This research aims to uncover whether KISS1 can mitigate H₂O₂‐triggered cell injury. HTR8 cells were pretreated with 250 μM H₂O₂ for 4 hours; the autophagic markers (Beclin‐1 and LC3B), cell viability, invasion and apoptosis were appraised. Real‐time quantitative polymerase chain reaction and Western blot trials were enforced for the valuation of KISS1 mRNA and protein levels. After si‐KISS1 transfection and 3‐MA manipulation, the aforesaid biological processes were reassessed for ascertaining the influences of repressed KISS1 in H₂O₂‐impaired HTR8 cells. Phosphoinositide 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was eventually estimated. H₂O₂ enhanced Beclin‐1 and LC3B expression, restricted cell viability, and invasion, and meanwhile caused apoptosis. The elevation of KISS1 evoked by H₂O₂ was observed in HTR8 cells. In addition, silencing KISS1 was distinctly annulled the function of H₂O₂ in HTR8 cells. Eventually, we observed that the repression of KISS1 triggered the activation of PI3K/AKT/mTOR in HTR8 cells under H₂O₂ management. The diverting research unveiled that KISS1 repression eased H₂O₂‐caused HTR8 cells injury via mediating PI3K/AKT/mTOR pathway.