RAMS11 Promotes CRC Through Mtor-Dependent Inhibition of Autophagy, Suppression of Apoptosis, and Promotion of Epithelial-Mesenchymal Transition

Normal Cells ◽

Mesenchymal Transition ◽

Migration Assay ◽

Diagnosis And Prognosis ◽

Non Coding Rnas ◽

Abstract BackgroundLong non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. MethodsThe expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro. To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR).ResultsOur results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction. ConclusionsIn sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.

RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition

Cancer Cell International ◽

10.1186/s12935-021-02023-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Md Zahirul Islam Khan ◽

Helen Ka Wai Law

Keyword(s):

Cell Lines ◽

Molecular Mechanisms ◽

Normal Cells ◽

Mesenchymal Transition ◽

Migration Assay ◽

Diagnosis And Prognosis ◽

Non Coding Rnas ◽

Abstract Background Long non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. Methods The expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro. To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR). Results Our results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction. Conclusions In sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.

RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition

10.21203/rs.3.rs-215699/v2 ◽

2021 ◽

Author(s):

Md Zahirul ISLAM KHAN ◽

Helen Ka-Wai LAW

Keyword(s):

Cell Lines ◽

Molecular Mechanisms ◽

Normal Cells ◽

Mesenchymal Transition ◽

Migration Assay ◽

Diagnosis And Prognosis ◽

Non Coding Rnas ◽

Abstract Background Long non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. Methods The expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro . To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR). Results Our results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction. Conclusions In sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.

Long Non-Coding RNAs in Epithelial-Mesenchymal Transition of Pancreatic Cancer

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.717890 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kenji Takahashi ◽

Kenzui Taniue ◽

Yusuke Ono ◽

Mikihiro Fujiya ◽

Yusuke Mizukami ◽

...

Keyword(s):

Tumor Cell ◽

Molecular Mechanisms ◽

Ductal Adenocarcinoma ◽

Potential Contribution ◽

Mesenchymal Transition ◽

Rna Molecules ◽

Invasion And Migration ◽

Non Coding Rnas ◽

Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

SOX10 induces epithelial–mesenchymal transition and contributes to nasopharyngeal carcinoma progression

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0160 ◽

2018 ◽

Vol 96 (3) ◽

pp. 326-331 ◽

Cited By ~ 4

Author(s):

Ping He ◽

Xiaojie Jin

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Mesenchymal Transition

Objective: The aim of this study was to investigate the role of SOX10 in nasopharyngeal carcinoma (NPC) and the underlying molecular mechanisms. Methods: The expression of SOX10 was initially assessed in human NPC tissues and a series of NPC cell lines through quantitative real-time PCR (qRT-PCR) and Western blot. Then, cell proliferation, cycle, migration, and the invasiveness of NPC cells with knockdown of SOX10 were examined by MTT, flow cytometry, and Transwell migration and invasion assays, respectively. Finally, nude mice tumorigenicity experiments were performed to evaluate the effects of SOX10 on NPC growth and metastasis in vivo. Results: SOX10 was significantly increased in NPC tissues and cell lines. In-vitro experiments revealed that loss of SOX10 obviously inhibited cell proliferation, migration, and invasiveness, as well as the epithelial–mesenchymal transition (EMT) process in NPC cells. In-vivo experiments further demonstrated that disrupted SOX10 expression restrained NPC growth and metastasis, especially in lung and liver. Conclusion: Taken together, our data confirmed the role of SOX10 as an oncogene in NPC progression, and revealed that SOX10 may serve as a novel biomarker for diagnosis of NPC, as well as a potential therapeutic target against this disease.

C1orf61 promotes hepatocellular carcinoma metastasis and affects the therapeutic response to sorafenib

10.21203/rs.3.rs-80702/v1 ◽

2020 ◽

Author(s):

You Yu ◽

Zhimeng Wang ◽

Zan Huang ◽

Xianying Tang ◽

Wenhua Li

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Therapeutic Response ◽

Mesenchymal Transition ◽

Molecular Events ◽

Carcinoma Metastasis ◽

Abstract Background C1orf61 is a specific transcriptional activator that is highly up-regulated during weeks 4–9 of human embryogenesis, the period in which most organs develop. We have previously demonstrated that C1orf61 acts as a tumor activator in human hepatocellular carcinoma (HCC) tumorigenesis and metastasis. However, the underlying molecular mechanisms of tumor initiation and progression in HCC remain obscure. Methods In this study, we demonstrated that the pattern of C1orf61 expression was closely correlated with metastasis in liver cancer cells. Gene expression profiling analysis indicated that C1orf61 regulated diverse genes related to cell growth, migration, invasion and epithelial-mesenchymal transition (EMT). Results Results showed that C1orf61 promotes hepatocellular carcinoma metastasis by inducing cellular EMT in vivo and in vitro. Moreover, C1orf61-induced cellular EMT and migration are involved in the activation of the STAT3 and Akt cascade pathways. We also found that C1orf61 was associated with HBV infection-induced cell migration in HCC. In addition, C1orf61 expression improved the efficacy of the anticancer therapy sorafenib in HCC patients. For the first time, we report a regulatory pathway by which C1orf61 promoted cancer cell metastasis and regulated the therapeutic response to sorafenib. Conclusions These findings increased our understanding of the molecular events that regulate metastasis and treatment in HCC.

Secreted Frizzled Related Protein 2 Modulates Epithelial–Mesenchymal Transition and Stemness via Wnt/β-Catenin Signaling in Choriocarcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000494862 ◽

2018 ◽

Vol 50 (5) ◽

pp. 1815-1831 ◽

Cited By ~ 7

Author(s):

Xianling Zeng ◽

Yafei Zhang ◽

Huiqiu Xu ◽

Taohong Zhang ◽

Yan Xue ◽

...

Keyword(s):

Cell Lines ◽

Molecular Mechanisms ◽

Underlying Mechanism ◽

Tumor Promoter ◽

Related Protein ◽

Mesenchymal Transition ◽

Jar Cells

Background/Aims: Choriocarcinoma (CC) is a highly aggressive gestational trophoblastic neoplasia; however, the underlying molecular mechanisms of its invasiveness and metastasis remain poorly understood. Human secreted frizzled-related protein 2 (SFRP2) could function as a tumor promoter or suppressor in different tumors, yet the role it plays in CC’s invasion and metastasis is thoroughly unclear. The current study was aimed to explore the function and underlying mechanism of SFRP2 in CC. Methods: The expression of SFRP2 in CC tissues was examined via immunohistochemistry. The methylation level and expression of SFRP2 in CC cell lines, JEG-3 and JAR were examined via bisulfite sequencing PCR (BSP), western blotting and quantitative RT-PCR. The biological role of increasing expressed SFRP2 through its promoter demethylation with 5-Aza-2’-deoxycytidine (5-Aza) was examined by a series of in vitro functional studies. Furthermore, lentivirus transfection technology was adopted to investigate the biological roles of SFRP2 knockdown in JEG-3 and JAR cells in vitro and in vivo. Moreover, its downstream signaling pathway was investigated. Results: SFRP2 was downregulated in CC tissues, and its expression was inversely related to its promoter hypermethylation frequency in JEG-3 and JAR cells. Increased SFRP2 through its promoter demethylation inhibited cell migration, invasion and colony formation in JEG-3 and JAR cells, whereas decreased SFRP2 reversed the epithelial-mesenchymal transition (EMT) process and stemness in JEG-3 and JAR cells both in vitro and vivo. Mechanistically, SFRP2 regulated the EMT and stemness of CC cell lines via canonical Wnt/β-catenin signaling, validated by the usage of a Wnt activator and inhibitor. Conclusion: The current study indicates that downregulated SFRP2 has potent tumor-promotive effects in CC through the modulation of cancer stemness and the EMT phenotype via activation of Wnt/β-catenin signaling in vitro and in vivo.

Upregulated Expression of SOX4 Is Associated with Tumor Growth and Metastasis in Nasopharyngeal Carcinoma

Disease Markers ◽

10.1155/2015/658141 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Si Shi ◽

Xiaolei Cao ◽

Miao Gu ◽

Bo You ◽

Ying Shan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Fate ◽

Molecular Mechanisms ◽

Critical Role ◽

Serum Starvation ◽

Ki 67 ◽

Mesenchymal Transition ◽

Migration Assay

SOX4, which belongs to the sex-determining region Y-related high-mobility group (SRY) box family, plays a critical role in embryonic development, cell fate decision, differentiation, and tumor development. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in China and Southeast Asia. However, the molecular mechanisms of this disease remain unknown. In the present study, we used immunohistochemistry to investigate the correlation between the expression of SOX4 with clinicopathologic variables as well as patients prognosis of NPC. We found overexpression of SOX4 was correlated with clinical stages, lymph node metastasis, and Ki-67 expression in NPC (P<0.05). Besides, patients who expressed higher levels of SOX4 had poorer survival rate (P<0.05). Then, in vitro studies, we took serum starvation-refeeding experiment and knocked down the expression of SOX4 with siRNA to demonstrate that SOX4 could promote proliferation of NPC nonkeratinizing cell line CNE2. The regulation of SOX4 on cell migration was determined by the transwell migration assay and wounding healing assay. Besides, we also found SOX4 could promote epithelial-mesenchymal transition (EMT) of CNE2 cells and decrease their cisplatin sensitivity. Our data suggested that SOX4 might play an important role in regulating NPC progression and would provide a potential therapeutic strategy for NPC.

SPP1 Promotes Enzalutamide Resistance and EMT Activation in CRPC Progression via PI3K/AKT and ERK1/2 Pathways

10.21203/rs.3.rs-533801/v1 ◽

2021 ◽

Author(s):

Xiaocong Pang ◽

Junling Zhang ◽

Xu He ◽

Yanlun Gu ◽

Wei Yu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Strong Relationship ◽

Castration Resistant Prostate Cancer ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Castration Resistant ◽

Abstract The bottleneck arising from castration-resistant prostate cancer (CRPC) treatment is its high metastasis potential and anti-androgen drug resistance, which severely affects survival time of prostate cancer (PCa) patients. In our previous study, we firstly revealed SPP1 was a potential hub signature for predicting metastatic CRPC (mCRPC) development. Herein, we integrated multiple databases to explore the association of SPP1 expression with prognosis, survival, metastatic levels in CRPC progression, and also investigated SPP1 expression in PCa tissues and cell lines. Next, PCa cell lines with overexpression or depletion of SPP1 were established to study the effect of SPP1 on enzalutamide sensitivity, and adhesion and migration of prostate cancer cell lines and further explore the underlying regulatory mechanisms. Bioinformatics analysis, PCR, immunohistochemical staining and western blot results suggested SPP1 upregulation had strong relationship with the malignant progression of CRPC. SPP1 knockdown repressed enzalutamide sensitivity, invasion and migration of prostate cancer cells in vitro. Importantly, upregulating SPP1 promoted, while silencing SPP1 attenuated epithelial-mesenchymal-transition (EMT). Our results further demonstrate that SPP1 overexpression maintains the activation of PI3K/AKT signaling and ERK1/2 pathways. Overall, our findings unraveled the functional role and clinical significance of SPP1 in PCa progression, and help to discover new potential targets against mCRPC.

Prognostic value of Mortalin correlates with roles in epithelial–mesenchymal transition and angiogenesis in lung adenocarcinoma

Carcinogenesis ◽

10.1093/carcin/bgab081 ◽

2021 ◽

Author(s):

Ziqi Meng ◽

Rui Zhang ◽

Xuwei Wu ◽

Meihua Zhang ◽

Songnan Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Malignant Phenotype ◽

Poor Overall Survival ◽

Mesenchymal Transition ◽

In Vivo Experiments ◽

Abstract Mortalin is involved in the malignant phenotype of many cancers. However, the specific molecular mechanisms involving Mortalin in lung adenocarcinoma remain unclear. In this study, we showed that both Mortalin mRNA and protein are overexpressed in lung adenocarcinoma. In addition, Mortalin overexpression was positively-correlated with poor overall survival. In vitro experiments showed that Mortalin silencing inhibited the proliferation, colony formation, and migration abilities of A549 and H1299 cells. Mortalin promotes EMT progression, angiogenesis, and tumor progression by activating the Wnt/β-catenin signaling pathway In vivo experiments further confirmed that Mortalin promoted malignant progression of lung adenocarcinoma. Taken together, our data suggest that Mortalin represents an attractive prognostic marker and therapeutic target in lung adenocarcinoma patients.

MiR-598 Suppresses Invasion and Migration by Negative Regulation of Derlin-1 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000489803 ◽

2018 ◽

Vol 47 (1) ◽

pp. 245-256 ◽

Cited By ~ 20

Author(s):

Fengming Yang ◽

Ke Wei ◽

Zhiqiang Qin ◽

Weitao Liu ◽

Chuchu Shao ◽

...

Keyword(s):

Cell Lines ◽

Luciferase Assay ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Over Expression ◽

Background/Aims: MicroRNAs regulate a wide range of biological processes of non-small cell lung cancer (NSCLC). Although miR-598 has been reported to act as a suppressor in osteosarcoma and colorectal cancer, the physiological function of miR-598 in NSCLC remains unknown. In this study, the role of miR-598 in NSCLC was investigated. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to estimate the expression of miR-598 and Derlin-1 (DERL1) in both NSCLC tissues and cell lines. Immunohistochemistry (IHC) analyzed the association between the miR-598 expression and epithelial-mesenchymal transition (EMT) hallmark genes (E-cadherin, Vimentin) by staining the tumors representative of the high- and low-expression groups. The effect of miR-598 and DERL1 on invasion and migration was determined in vitro using transwell and wound-healing assays. The molecular mechanism underlying the relevance between miR-598 and DERL1 was elucidated by luciferase assay and Western blot. Western blot assessed the expression levels of EMT hallmark genes in cell lines. Xenograft tumor formation assay was conducted as an in vivo experiment. Results: In this study, a relatively low level of miR-598 and high DERL1 expressions were found in NSCLC specimens and cell lines. IHC results established a positive correlation between the miR-598 expression and E-cadherin and a negative with Vimentin. DERL1 was verified as a direct target of miR-598 by luciferase assay. In vitro, the over-expression of miR-598 negatively regulated DERL1 and EMT for the suppression of invasion and migration. In vivo, the over-expression of miR-598 could inhibit tumor cell metastasis in NSCLC. Conclusions: These findings for the first time revealed that miR-598, as a tumor suppressor, negatively regulate DERL1 and EMT to suppress the invasion and migration in NSCLC, thereby putatively serving as a novel therapeutic target for NSCLC clinical treatment.