The role of leucine-rich alpha-2-glycoprotein-1 in proliferation, migration, and invasion of tumors

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

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LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression

Open Life Sciences ◽

10.1515/biol-2021-0002 ◽

2021 ◽

Vol 16 (1) ◽

pp. 1-13

Author(s):

Weiwei Liu ◽

Dongmei Yao ◽

Bo Huang

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Nude Mouse Model ◽

Western Blot Assay ◽

Non Coding Rna ◽

Long Non Coding Rna

Abstract Cervical cancer (CC) is a huge threat to the health of women worldwide. Long non-coding RNA plasmacytoma variant translocation 1 gene (PVT1) was proved to be associated with the development of diverse human cancers, including CC. Nevertheless, the exact mechanism of PVT1 in CC progression remains unclear. Levels of PVT1, microRNA-503 (miR-503), and ADP ribosylation factor-like protein 2 (ARL2) were measured by quantitative reverse transcription-polymerase chain reaction or western blot assay. 3-(4,5)-Dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) and flow cytometry were used to examine cell viability and apoptosis, respectively. For migration and invasion detection, transwell assay was performed. The interaction between miR-503 and PVT1 or ARL2 was shown by dual luciferase reporter assay. A nude mouse model was constructed to clarify the role of PVT1 in vivo. PVT1 and ARL2 expressions were increased, whereas miR-503 expression was decreased in CC tissues and cells. PVT1 was a sponge of miR-503, and miR-503 targeted ARL2. PVT1 knockdown suppressed proliferation, migration, and invasion of CC cells, which could be largely reverted by miR-503 inhibitor. In addition, upregulated ARL2 could attenuate si-PVT1-mediated anti-proliferation and anti-metastasis effects on CC cells. Silenced PVT1 also inhibited CC tumor growth in vivo. PVT1 knockdown exerted tumor suppressor role in CC progression via the miR-503/ARL2 axis, at least in part.

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Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

Scientific Reports ◽

10.1038/s41598-020-80152-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tiantian Tang ◽

Guiying Wang ◽

Sihua Liu ◽

Zhaoxue Zhang ◽

Chen Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

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Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells

Cell Death Discovery ◽

10.1038/s41420-021-00482-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Oleg Shuvalov ◽

Alyona Kizenko ◽

Alexey Petukhov ◽

Olga Fedorova ◽

Alexandra Daks ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Reproductive System ◽

Seminal Fluid ◽

Cancer Development ◽

Migration And Invasion ◽

Malignant Cells ◽

Cancer Testis

AbstractCancer-testicular Antigens (CTAs) belong to a group of proteins that under normal conditions are strictly expressed in a male’s reproductive tissues. However, upon malignisation, they are frequently re-expressed in neoplastic tissues of various origin. A number of studies have shown that different CTAs affect growth, migration and invasion of tumor cells and favor cancer development and metastasis. Two members of the CTA group, Semenogelin 1 and 2 (SEMG1 and SEMG2, or SEMGs) represent the major component of human seminal fluid. They regulate the motility and capacitation of sperm. They are often re-expressed in different malignancies including breast cancer. However, there is almost no information about the functional properties of SEMGs in cancer cells. In this review, we highlight the role of SEMGs in the reproductive system and also summarize the data on their expression and functions in malignant cells of various origins.

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The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer

Journal of International Medical Research ◽

10.1177/03000605211014363 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110143

Author(s):

Mingcui Zang ◽

Xun Guo ◽

Manqiu Chen

Keyword(s):

Prostate Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Prostate Tumorigenesis ◽

Expression Levels ◽

Matrigel Invasion ◽

Tensin Homolog ◽

Docetaxel Treatment ◽

Induced Apoptosis

Objective MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). Methods The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3ʹ untranslated region (3ʹ UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. Results Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3ʹ UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. Conclusions miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.

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Role of ARID1A in the Regulation of Human Trophoblast Migration and Invasion

Reproductive Sciences ◽

10.1007/s43032-021-00686-0 ◽

2021 ◽

Author(s):

Meiyuan Jin ◽

Shouying Xu ◽

Jiayong Li ◽

Lu Li ◽

Chao Tang

Keyword(s):

Migration And Invasion ◽

Human Trophoblast ◽

Trophoblast Migration

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Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Integrative Cancer Therapies ◽

10.1177/15347354211031646 ◽

2021 ◽

Vol 20 ◽

pp. 153473542110316

Author(s):

Liang Wang ◽

Lei Xu ◽

Yu Wang

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Dna Methyltransferase ◽

Cutaneous Squamous Cell Carcinoma ◽

Migration And Invasion ◽

Dependent Manner ◽

Concentration Gradients ◽

A431 Cells

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

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Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

Cell Death and Disease ◽

10.1038/s41419-021-03626-7 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Xiaoguang Gu ◽

Jianan Zhang ◽

Yajuan Ran ◽

Hena Pan ◽

JinHong Jia ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Biological Effects ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Casein Kinase 1 ◽

Mouse Xenograft Model ◽

Hcc Cells

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.

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