Mulberry fruit polysaccharides alleviate diethylnitrosamine/phenobarbital-induced hepatocarcinogenesis in vivo: the roles of cell apoptosis and inflammation

Abstract Background Myocardial dysfunction caused by sepsis (SIMD) leads to high mortality in critically ill patients. We investigated the function and mechanism of long non-coding RNA MAPKAPK5-AS1 (lncRNA MAPKAPK-AS1) on lipopolysaccharide (LPS)-induced inflammation response in vivo and in vitro. Method Male SD rats were utilized for in vivo experiments. Rat cardiomyocytes (H9C2) were employed for in vitro experiments. Western blotting was employed to measure protein expression, and RT-PCR was performed to measure mRNA expression of inflammation factors. TUNEL and flow cytometry were carried out to evulate cell apoptosis. Result The results showed that the expression of MAPKAPK5-AS1 was increased, while the expression of miR-124-3p was decreased in the inflammatory damage induced by LPS in vivo and in vitro. Knockdown of MAPKAPK5-AS1 reduced LPS-induced cell apoptosis and inflammation response, while overexpression of miR-124-3p weakened the effects of MAPKAPK5-AS1 knockdown on LPS-induced cell apoptosis and inflammation response. Moreover, miR-124-3p was identified as a downstream miRNA of MAPKAPK5-AS1, and E2F3 was a target of miR-214-3p. MAPKAPK5-AS1 knockdown increased the expression of miR-124-3p, while miR-124-3p overexpression reduced the expression of MAPKAPK5-AS1. In addition, miR-124-3p was found to downregulate E2F3 expression in H9C2 cells. Conclusion MAPKAPK5-AS1/miR-124-3p/E2F3 axis regulates LPS-related H9C2 cell apoptosis and inflammatory response.

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Corilagin Inhibits Esophageal Squamous Cell Carcinoma by Inducing DNA Damage and Down-Regulation of RNF8

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190307120811 ◽

2019 ◽

Vol 19 (8) ◽

pp. 1021-1028 ◽

Cited By ~ 3

Author(s):

Fanghua Qiu ◽

Lifang Liu ◽

Yu Lin ◽

Zetian Yang ◽

Feng Qiu

Keyword(s):

Cell Proliferation ◽

Dna Damage ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cell Apoptosis ◽

Cell Counting ◽

Antitumor Effects

Background:Esophageal squamous cell carcinoma (ESCC), the most prevalent histologic subtype of esophageal cancer, is an aggressive malignancy with poor prognosis and a high incidence in the East. Corilagin, an active component present in Phyllanthus niruri L., has been shown to suppress tumor growth in various cancers. However, the effects of corilagin on ESCC and the mechanisms for its tumor suppressive function remain unknown.Methods:Cell proliferation was measured by Cell Counting Kit-8 assay and colony formation assays. Annexin V/PI double-staining was performed to assess cell apoptosis. Immunofluorescence staining and western blotting were used to evaluate the protein expression. A xenograft mice model was used to assess the in vivo antitumor effects of corilagin alone or in combination with cisplatin.Results:We for the first time showed that corilagin was effectively able to inhibit ESCC cell proliferation and induce cell apoptosis. Additionally, our results validated its antitumor effects in vivo using a xenograft mouse model. Mechanistically, we found that corilagin caused significant DNA damage in ESCC cells. We found that corilagin could significantly attenuate the expression of the E3 ubiquitin ligase RING finger protein 8 (RNF8) through ubiquitin-proteasome pathway, leading to the inability of DNA damage repair response and eventually causing cell apoptosis. Furthermore, we also showed that corilagin substantially enhanced the antitumor effects of chemotherapy drug cisplatin both in vitro and in vivo.Conclusion:Our results not only provided novel and previously unrecognized evidences for corilagin-induced tumor suppression through inducing DNA damage and targeting RNF8 in ESCC, but also highlighted that corilagin might serve as an adjunctive treatment to conventional chemotherapeutic drugs in ESCC patients.

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LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00275-8 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

An Yang ◽

Xin Liu ◽

Ping Liu ◽

Yunzhang Feng ◽

Hongbo Liu ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Apoptosis ◽

Gastric Cancer Cell ◽

Gastric Cancer Cells ◽

Gastric Cancer Cell Lines ◽

Development Of Gastric Cancer

Abstract Background Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. Methods The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. Results UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. Conclusions UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

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TRIM27-mediated ubiquitination of PPARγ promotes glutamate-induced cell apoptosis and inflammation

Experimental Cell Research ◽

10.1016/j.yexcr.2020.112437 ◽

2020 ◽

pp. 112437

Author(s):

Yong Hao ◽

Shuwei Bai ◽

Jing Peng ◽

Ronghua Hong ◽

Jie Ding ◽

...

Keyword(s):

Cell Apoptosis ◽

Apoptosis And Inflammation

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Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

Molecular Medicine ◽

10.1186/s10020-021-00332-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Jian-Ping Zhang ◽

Wei-Jing Zhang ◽

Miao Yang ◽

Hua Fang

Keyword(s):

Cell Apoptosis ◽

Ischemia Reperfusion Injury ◽

Glycogen Synthase ◽

Ischemia Reperfusion ◽

Inflammatory Factors ◽

Therapeutic Effects ◽

Protective Effects ◽

Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

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Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

Journal of Biological Research-Thessaloniki ◽

10.1186/s40709-021-00145-6 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Jingpeng Wang ◽

Shuyuan Li ◽

Gaofeng Zhang ◽

Huihua Han

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Volatile Anesthetic ◽

Tumor Formation ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

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DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

Cell Death and Disease ◽

10.1038/s41419-021-03796-4 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Yixin Tong ◽

Yuan Huang ◽

Yuchao Zhang ◽

Xiangtai Zeng ◽

Mei Yan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Cell Apoptosis ◽

Downstream Target ◽

Normal Tissues ◽

Physiological Processes ◽

Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

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Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2

Cell Death Discovery ◽

10.1038/s41420-021-00402-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yu Wang ◽

Liming Zhu ◽

Mei Guo ◽

Gang Sun ◽

Kun Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cell ◽

Cell Apoptosis ◽

B Cell Lymphoma ◽

Histone Methyltransferase ◽

Chemotherapeutic Agents ◽

Cancer Cell Apoptosis ◽

Active Transcription

AbstractWHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. In this study, we revealed how WHSC1 regulates tumorigenesis and chemosensitivity of colorectal cancer (CRC). Our data showed that WHSC1 as well as H3K36me2 were highly expressed in clinical CRC samples, and high WHSC1 expression is associated with poorer prognosis in CRC patients. WHSC1 reduction promoted colon cancer cell apoptosis both in vivo and in vitro. We found that B cell lymphoma-2 (BCL2) expression, an anti-apoptotic protein, is markedly decreased in after WHSC1 depletion. Mechanistic characterization indicated that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level. What’s more, our study indicated that WHSC1 depletion promotes chemosensitivity in CRC cells. Together, our results suggested that WHSC1 and H3K36me2 modification might be optimal therapeutic targets to disrupt CRC progression and WHSC1-targeted therapy might potentially overcome the resistance of chemotherapeutic agents.

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Extract of Pogostemon cablin Possesses Potent Anticancer Activity against Colorectal Cancer Cells In Vitro and In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9758156 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Ju-Huei Chien ◽

Shan-Chih Lee ◽

Kai-Fu Chang ◽

Xiao-Fan Huang ◽

Yi-Ting Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Apoptosis ◽

Cycle Arrest ◽

Anticancer Effects ◽

Pogostemon Cablin ◽

Colorectal Cancer Cells ◽

Potential Applicability ◽

Cancer Suppression

Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.

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