• Long noncoding RNA
• biomarker
• cholangiocarcinoma
• hepatocellular carcinoma
• liver cancer

• Humans
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/metabolism
• RNA, Long Noncoding/genetics
• Up-Regulation
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Male
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Female
• Middle Aged
• Serine Proteases

• (sub)genotypes
• hepatitis B virus
• hepatocellular carcinoma
• oncogenic pathways
• viral oncogenesis

• Humans
• Hepatitis B virus/genetics
• Proteomics
• Genotype
• Cell Line, Tumor
• Signal Transduction
• Africa South of the Sahara
• Proteome
• rhoC GTP-Binding Protein/metabolism
• rhoC GTP-Binding Protein/genetics
• Carcinoma, Hepatocellular/virology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/genetics
• Transfection
• Liver Neoplasms/virology
• Liver Neoplasms/metabolism
• Liver Neoplasms/genetics
• Hepatitis B/virology
• Hepatitis B/metabolism
• Hepatitis B/genetics

• https://cansa.org.za/, accessed on 1 January 2023 Cancer Association of South Africa

• Breast cancer
• Exosomes
• Obesity
• The metabolic phenotype

• Tehran University of Medical Sciences and Health Services

• Apoptosis
• Breast cancer
• Extracellular vesicles
• Obesity
• Obesity phenotypes

• Humans
• Female
• Triple Negative Breast Neoplasms
• Overweight/complications
• Overweight/metabolism
• Matrix Metalloproteinase 2/metabolism
• Tumor Suppressor Protein p53
• Obesity/metabolism
• Extracellular Vesicles/metabolism

Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A ∆50 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease. Some patients with PS carry other LMNA mutations and are named “HGPS-like” patients. They produce progerin and/or other truncated prelamin A isoforms (∆35 and ∆90). We previously found that MG132, a proteasome inhibitor, induced progerin clearance in classical HGPS through autophagy activation and splicing regulation. Here, we show that MG132 induces aberrant prelamin A clearance and improves cellular phenotypes in HGPS-like patients’ cells other than those previously described in classical HGPS. These results provide preclinical proof of principle for the use of a promising class of molecules toward a potential therapy for children with HGPS-like or classical HGPS.

Esophageal cancer (EC) is a malignant tumor with high mortality. Correlations have been found between the expression level of tropomyosin 3 (TPM3) and the depth of tumor invasion, lymph node metastasis, and the 5-year survival rate. However, the specific mechanisms underlying EC remain unclear.

Stably transfected TPM3-overexpresing and TPM3-knockdown esophageal squamous cell carcinoma (ESCC) cell lines (ECa109 and EC9706) were constructed, and the association between TPM3 and the proliferation, invasion, and migration of ESCC was investigated using molecular biology methods. The associations between TPM3 and matrix metalloproteinase (MMP)2/9 or epithelial-mesenchymal transition (EMT)-related proteins were verified, and the potential tumor-promoting mechanism was explored by Gelatin Zymography Experiment.

TPM3 was found to promote the proliferation, migration, and metastatic potential of ESCC in vivo and in vitro, and stimulate the expression of MMP2/9 and certain EMT markers other than E-cadherin. The replenishment of MMP2/9 restored the malignant behavior of ESCC caused by TPM3. A gelatinase assay showed that the expression of TPM3 was related to the activity of MMP9.

TPM3 promoted proliferation, migration, and metastatic potential in EC cells. Additionally, TPM3 promoted the EMT process. This function may be achieved via the regulation the expression of MMP2/9.

• Tropomyosin 3 (TPM3)
• epithelial-mesenchymal transition (EMT)
• esophageal cancer (EC)
• matrix metalloproteinase 2 (MMP2)
• matrix metalloproteinase 9 (MMP9)

• Cancer therapy
• Extracellular matrix
• Matrix metalloproteinases
• Matrix metalloproteinases inhibitors
• Tumor microenvironment
• Tumorigenesis

• Animals
• Humans
• Matrix Metalloproteinase Inhibitors/therapeutic use
• Matrix Metalloproteinases/metabolism
• Neoplasms/drug therapy
• Neoplasms/metabolism
• Neoplasms/pathology

• Breast cancer
• MAPK and NFKβ signaling pathways
• Matrix metalloproteinases
• Migration
• PI3K
• Tamoxifen resistance

• Antineoplastic Agents, Hormonal/therapeutic use
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Drug Resistance, Neoplasm
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Metalloproteases/metabolism
• Mitogen-Activated Protein Kinase 1/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Tamoxifen/therapeutic use

In recent years, major discoveries have indicated that Ras homology family member C (RHOC) is involved in the occurrence and pathological progression of a number of malignant tumours; nevertheless, the role served by RHOC in glioma remains unclear. The present study aimed to gain further insight into the biological function and expression of RHOC in human glioma based on the Chinese Glioma Genome Atlas (CGGA). The current study analysed ~1,000 glioma samples from the CGGA. First, RHOC expression was analysed according to the clinical features associated with the prognosis of glioma, such as clinical stage, histological type and age. Second, the Kaplan-Meier method was used, revealing that the survival rate of patients with glioma with high RHOC expression was significantly lower than that of patients with low RHOC expression. Receiver operating characteristic curve analysis indicated that RHOC had moderate diagnostic value for patients with glioma. Gene set enrichment analysis indirectly indicated that RHOC mainly participated in the pathological mechanism of glioma through p53, extracellular matrix receptor interaction and focal adhesion. Finally, the aforementioned results were further verified using The Cancer Genome Atlas data and reverse transcription-quantitative PCR technology. To the best of our knowledge, the present study was the first comprehensive in-depth analysis of RHOC, revealing the potential value of RHOC as a novel oncogene in glioma. The current study provided a novel potential biomarker for the diagnosis and prognosis of glioma, and re-examined the pathological mechanism of glioma from a new perspective.

• Ras homology family member C
• early diagnosis
• glioma
• treatment

• Allogeneic bone marrow transplantation
• Engraftment
• Metalloproteinase-3
• Tonsil-derived mesenchymal stem cells
• Type IV collagen

Ras homolog family member C (RhoC) is an important component of intracellular signal transduction and its overexpression has been reported to be involved in regulating tumor proliferation, invasion, and metastasis in various malignant tumors. However, its role and underlying mechanism in oral squamous cell carcinoma (OSCC) still remain obscure. In our study, RhoC expression, its relation with clinical stages, and survival rate in OSCC were analyzed using datasets from The Cancer Genome Atlas (TCGA). Next, a RhoC knockdown cell model was established in vitro, and the effects of RhoC knockdown in OSCC cells were detected by the MTT assay, colony formation assay, transwell invasion assay, scratch assay, and F-actin phalloidin staining. An in vivo tongue-xenografted nude mouse model was established to measure the effects of knockdown of RhoC on tumor cell growth and lymph node metastasis. A mechanism study was conducted by real-time PCR and immunocytochemistry. The results of TCGA analysis showed that RhoC was overexpressed in OSCC tumor tissues. In vitro assays indicated that knockdown of RhoC did not have much effect on OSCC cell growth but significantly suppressed cell colony formation, invasion, and migration abilities, and F-actin polymerization was also reduced. The tongue-xenografted in vivo model demonstrated that knockdown of RhoC suppressed OSCC cell growth and inhibited metastasis to the superficial cervical lymph nodes. Further mechanism studies showed that knockdown of RhoC downregulated HMGA2 expression, and HMGA2 expression was highly correlated with RhoC expression in OSCC tumor tissues via the analysis of TCGA datasets. Overall, our study showed that knockdown of RhoC inhibited OSCC cells invasion and migration in vitro and OSCC cell growth and lymph node metastasis in vivo. Moreover, the potential mechanisms involved in these activities may be related to the regulation of HMGA2 expression. The RhoC gene could serve as a promising therapeutic target for OSCCs in the future.

The aim of the present study was to determine the effect of microRNA (miR)-155-5p on the expression of testican-1 (SPOCK1) and the invasion and migration of prostate cancer cells in vitro. Bioinformatics analysis and molecular biology assays revealed that SPOCK1 may be a direct target gene of miR-155-5p. In addition, a negative correlation was identified between SPCOK1 and miR-155-5p expression in prostate tumor tissues and cell lines. miR-155-5p mimic transfection inhibited SPOCK1 expression in PC3 cells and decreased cell migration and invasion abilities, while the expression of vimentin, N-cadherin, E-cadherin, β-catenin, matrix metalloproteinase (MMP)3 and MMP9 was upregulated. In summary, SPOCK1 was found to be a target gene of miR155-5p in prostate cancer, and miR-155-5p acts as a tumor-suppressor gene and may inhibit SPOCK1-mediated prostate cancer progression.

• miR-155-5p
• migration
• prostate cancer
• testican-1F

• EMT
• Wnt/β-catenin
• colorectal cancer
• metastasis
• sanguinarine

• xtr0118022 Fundamental Research Funds for the Central Universities
• 81773772 National Natural Science Foundation of China
• Fundamental Research Funds for the Central Universities
• National Natural Science Foundation of China

Tumor heterogeneity results in differential response to therapy due to the existence of plastic tumor cells, called cancer stem cells (CSCs), which exhibit the property of resistance to therapy, invasion and metastasis. These cells have a distinct, signaling network active at every stage of progression. It is difficult to envisage that the CSCs will have a unique set of signaling pathways regulating every stage of disease progression. Rather, it would be easier to believe that a single pivotal pathway having significant contribution at every stage, which can further turn on a battery of signaling mechanisms specific to that stage, would be instrumental in regulating the signaling network, enabling easy transition from one state to another. In this context, we discuss the role of RhoC which has contributed to several phenotypes during tumor progression.

RhoC (Ras homolog gene family member C) has been widely reported to regulate actin organization. It has been shown to impact the motility of cancer cells, resultantly affecting invasion and metastasis, and has contributed to carcinoma progression of the breast, pancreas, lung, ovaries and cervix, among several others. The most interesting finding has been its indispensable role in metastasis. Also, it has the ability to modulate various other phenotypes like angiogenesis, motility, invasion, metastasis, and anoikis resistance. These observations suggest that RhoC imparts the plasticity required by tumor cells to exhibit such diverse functions based on microenvironmental cues. This was further confirmed by recent reports which show that it regulates cancer stem cells in breast, ovary and head and neck cancers. Studies also suggest that the inhibition of RhoC results in abolition of advanced tumor phenotypes.

Our review throws light on how RhoC, which is capable of modulating various phenotypes may be the apt core signaling candidate regulating disease progression. Additionally, mice studies show that RhoC is not essential for embryogenesis, giving scope for its development as a possible therapeutic target. This review thus stresses on the need to understand the protein and its functioning in greater detail to enable its development as a stem cell marker and a possible therapeutic target.

• Cancer stem cells
• RhoC
• Therapy resistance
• Tumor phenotypes

By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms.

MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective.

The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination.

MMP1, MMP9, MMP10, MMP11, and MMP13 were almost universally upregulated across all cancers, with significant (p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3, MMP7, MMP12 and MMP14) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2, MMP7, MMP23B, MMP27 and MMP28) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC’s > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma.

Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer.

The online version of this article (10.1186/s12885-019-5768-0) contains supplementary material, which is available to authorized users.

• Biomarkers
• Diagnosis
• Gene expression
• MMPs
• Matrix metalloproteases
• Prognosis
• Survival
• TCGA

• Breast cancer
• Kaempferol
• Mechanism

To clarify the underlying mechanism of formin-like 3 (FMNL3) in the promotion of colorectal carcinoma (CRC) cell invasion.

The in vitro biological function analyses of FMNL3 were performed by gain- and loss-of function approaches. Changes in the F-actin cytoskeleton were detected by the technologies of phalloidin-TRITC labeling and confocal microscopy. The signaling pathway mediated by FMNL3 was explored by western blot, gelatin zymograph assay, co-immunoprecipitation (co-IP), immunofluorescence co-localization, and glutathione S-transferase (GST) pull-down assay.

The in vitro experimental results showed that FMNL3 significantly promoted the proliferation, invasion, and migration of CRC cells (P < 0.05 and P < 0.01). Moreover, FMNL3 regulated the remodeling of actin-based protrusions such as filopodia and lamellipodia in a RhoC-dependent manner. The western blot and gelatin zymograph assay results indicated that FMNL3 was involved in the RhoC/ focal adhesion kinase (FAK) pathway and acted as an effector of RhoC to activate the downstream signaling of p-FAK as well as p-MAPK and p-AKT. This resulted in the increased expression of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF), and the subsequent promotion of CRC cell invasion. The results of TAE226, U0126 or Ly294002 treatment confirmed an essential role of FMNL3 in activation of the RhoC/FAK pathway and the subsequent promotion of CRC invasion. Co-IP, co-localization and GST pull-down assays showed the direct interaction of FMNL3 with RhoC in vivo and in vitro.

FMNL3 regulates the RhoC/FAK signaling pathway and RhoC-dependent remodeling of actin-based protrusions to promote CRC invasion.

• Formin-like 3
• Colorectal carcinoma
• Invasion
• RhoC/FAK pathway
• Actin assembly

• Actins/metabolism
• Cell Adhesion/drug effects
• Cell Line, Tumor
• Cell Movement/drug effects
• Colorectal Neoplasms/pathology
• Enzyme Inhibitors/pharmacology
• Focal Adhesion Kinase 2/genetics
• Focal Adhesion Kinase 2/metabolism
• Formins
• HEK293 Cells
• Humans
• Neoplasm Invasiveness/pathology
• Proteins/antagonists & inhibitors
• Proteins/genetics
• Proteins/metabolism
• RNA, Small Interfering/metabolism
• Signal Transduction/drug effects
• rhoC GTP-Binding Protein/metabolism

• AFAP1-AS1
• Biomarker
• Carcinogene
• Carcinoma
• Long non-coding RNA

It has been reported that ribophorin II (RPN2) expression is increased in many cancers, but the role of RPN2 in nasopharyngeal carcinoma (NPC) remains unclear.

This study found that the expression of RPN2 is increased dramatically in NPC tissues of patients compared with that in the adjacent normal tissues. This study attempted at understanding the effect of siRNA-RPN2 treatment on the migration and invasion of NPC cell lines CNE2 and HNE1.

RT-PCR and Western blotting showed that RPN2 was highly expressed in CNE2 and HNE1 cells. siRNA-RPN2 treatment significantly inhibited cell viability at 24 and 48 h compared with the control group. Results of the transwell assay showed that, compared to the control groups, migration and invasion of the cells treated with siRNA-RPN2 decreased markedly. In addition, compared to the control groups, caspase-3, caspase-9, and E-cadherin expression levels increased and MMP 2 expression decreased significantly in the siRNA-RPN2-treated group. Phosphorylation of AKT and PI3K was also inhibited after siRNA-RPN2 treatment.

siRNA-RPN2 can effectively inhibit the invasion and migration of human NPC cells via AKT/PI3K signaling. This can serve as a novel strategy for NPC treatment.

• MMP2
• MMP9
• invasion
• migration
• nasopharyngeal carcinoma
• siRNA-RPN2

• cadherin 11
• cadherin 6
• cluster of differentiation 44
• metastasis
• oral squamous cell carcinoma
• prognosis

• biosensors
• medical imaging/imaging nanoparticles
• therapeutics

• MMP3
• MMP9
• adipocytes
• exosomes
• lung cancer