The pan-cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target.

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

Budding uninhibited by benzimidazoles 1 might be a poor prognosis biomarker promoting the progression of papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most widespread malignant tumors of the endocrine system, with a high incidence. Budding uninhibited by benzimidazoles 1 (BUB1), one of the spindle assembly checkpoint (SAC) genes, is a multitask protein kinase required for eukaryotic chromosome segregation. Although BUB1 has been explored in several types of cancer, its biological role and molecular mechanisms in PTC remain unclear. METHODS: In this study, we performed an examination of four public datasets along with local PTC cohorts and discovered that BUB1 was elevated in PTC compared to non-cancer tissues. High BUB1 expression was linked with the status of BRAFV600E , RAS, and TERT after statistical analysis. RESULTS: Clinically, BUB1 is associated with a variety of clinicopathological features in PTC patients. Interestingly, analysis of the TCGA database showed that BUB1 was closely associated with poor prognosis of PTC and significantly correlated with PFS. As determined by regression analysis, BUB1, and T stage were independent predictors of PTC and were related to BRAFV600E and lymph node metastatic status. By RT-qPCR, BUB1 was considerably overexpressed in PTC cell lines in comparison with normal thyroid epithelial cells. CONCLUSION: We confirmed that the knockdown of BUB1 in BCPAP and TPC1 cell lines significantly inhibited cell proliferation, cloning, and migration in vitro experiments. These results imply that BUB1 may be a significant oncogenic gene that is directly associated with the prognosis of PTC and may represent a future target for therapeutic intervention.

Phospholipase C Delta 3 inhibits apoptosis and promotes proliferation, migration, and invasion of thyroid cancer cells via Hippo pathway.

In recent decades, the incidence of thyroid cancer (TC) has rapidly increased, leading us to explore the complex underlying mechanisms. We identified the gene Phospholipase C Delta 3 (PLCD3) as a potential oncogene in TC by conducting the whole transcriptome sequencing. Our study is to understand the oncogenic role of PLCD3 in TC. We verified the overexpression of PLCD3 in TC from The Cancer Genome Atlas, Gene Expression Omnibus databases, and a locally validated cohort. Clinical correlation analysis showed that PLCD3 expression was related to histological type, T stage, lymph node metastasis (LNM), and disease stage. The high expression of PLCD3 could be a distinguishing factor for TC and its LNM. The biological function was examined using small interfering RNA-transfected TC cell lines. Silenced PLCD3 could inhibit colony formation, migration, and invasion ability and promote apoptosis of TC cell lines. PLCD3 silencing reversed the epithelial-mesenchymal transition but induced the apoptotic progress. Further exploration revealed that PLCD3 might be associated with critical genes of the Hippo pathway. The expressions of RHOA, YAP1/TAZ, and their downstream targets were decreased significantly when PLCD3 was down-regulated. YAP1 overexpression rescued the tumor-suppressive effect caused by PLCD3 silencing. This study demonstrates that PLCD3 is an oncogene that supports tumorigenesis and progression in TC, and PLCD3 may be a potential target gene for TC treatment.

Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up-regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf-like PTC patients with higher IMUP expression had shorter disease-free survival. The biological function of IMUP in PTC cell lines (KTC-1 and TPC-1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis-related molecules were identified by real-time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down-regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future. SIGNIFICANCE OF THE STUDY: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti-oncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins.

LRRC52-AS1 is associated with clinical progression and regulates cell migration and invasion in papillary thyroid cancer.

The incidence of thyroid cancer has increased in recent decades. The potential molecular mechanisms of papillary thyroid cancer (PTC) are still to be uncovered. In recent years, a number of studies reported that LRRC super family members are up-regulated in cancer cells. Cancer cells can experience a feature change from an epithelial to a mesenchymal phenotype, which is called epithelial-mesenchymal transition (EMT) during cancer progression. We found that LRRC52-AS1 is highly expressed in PTC cell lines rather than normal tissues and this observation was consistent with The Cancer Genome Atlas (TCGA) cohort. In a word, LRRC52-AS1 is associated with clinical progression in papillary thyroid cancer. In vitro experiments showed that knocking down LRRC52-AS1 significantly decreased the migration and invasion of the PTC cell lines (BCPAP and TPC). Meanwhile, LRRC52-AS1 may influence the progress of papillary thyroid cancer via mesenchymal markers N-cadherin, vimentin and TAZ. The LRRC52-AS1 gene is up-regulated in papillary thyroid cancer, and knockdown of LRRC52-AS1 could restrain cellular migration, and invasion in vitro. This study indicated that LRRC52-AS1 is a gene associated with PTC and might become a potential therapeutic target in PTC.

Downregulating integrin subunit alpha 7 (ITGA7) promotes proliferation, invasion, and migration of papillary thyroid carcinoma cells through regulating epithelial-to-mesenchymal transition.

Thyroid cancer is one of the common malignancies of the endocrine system and the number of thyroid cancer cases is increasing constantly. Significant work has focused on the molecular mechanisms of thyroid cancer, but many mechanisms remain undiscovered. In this study, we employed a comprehensive analysis of whole-transcriptome resequencing derived from paired papillary thyroid cancer (PTC) and normal thyroid tissues. We performed a massive parallel whole-transcriptome resequencing of matched PTC and normal thyroid tissues in 19 patients and found that integrin subunit alpha 7 (ITGA7) was downregulated in thyroid tumor tissues, but the function of ITGA7 in this cancer is still unclear. We also discovered that ITGA7 gene in thyroid cancer tissues was downregulated compared to paired adjacent non-tumor tissues by real-time quantitative polymerase chain reaction. After transfection with small interfering RNA to knock down ITGA7, the abilities of colony formation, proliferation, migration, and invasion were enhanced in PTC cell lines (TPC1 and KTC-1). Meanwhile, ITGA7 knockdown decreased apoptotic cell death in thyroid cells but promoted the expressions of N-cadherin and vimentin and decreased E-cadherin expression by epithelial-to-mesenchymal transition, which may induce invasion and migration. In conclusion, these results indicated that ITGA7 is involved in the progress of PTC and might act as a tumor suppressor gene.

Uridine phosphorylase 1 associates to biological and clinical significance in thyroid carcinoma cell lines.

Thyroid cancer incidence has been continuity increasing worldwide. Uridine phosphorylase 1 (UPP1) is a protein-coding gene and has been detected that UPP1 was the higher expression in many solid malignancies, just as head and neck cancers, breast cancer, compared with paired normal tissue. But the act of UPP1 in thyroid cancer is not explicit. In this article, we investigate the function of UPP1 expression in thyroid cancer. The Cancer Genome Atlas (TCGA) unpaired thyroid cancer and normal RNA-seq data were downloaded, and our paired thyroid cancer and normal samples were analysed by a polymerase chain reaction. The expression of UPP1 was regulated by transfected small interfering RNA, and the function of UPP1 was determined via migration, invasion and cell proliferation assays. Western blot assay was achieved to determine the UPP1 expression correlates with the function of 5-FU regulate epithelial-mesenchymal transition. The significant upregulation of UPP1 in thyroid cancer tissues compared with normal thyroid tissues was revealed by our data and TCGA data. UPP1 overexpression was significantly correlated with lymph node metastasis, tumour stage and tumour size. In the cell, experiments showed that UPP1 low expression significantly suppressed the migration, invasion and proliferation. Western blot assay proves the effect of UPP1 expression on 5-FU regulates epithelial-mesenchymal transition pathway. UPP1 plays a crucial oncogene in thyroid cancer. Our findings indicate that UPP1 might be a biomarker of thyroid cancer and may act by regulating epithelial-mesenchymal transition (EMT).

COPB2 is up-regulated in breast cancer and plays a vital role in the metastasis via N-cadherin and Vimentin.

Breast cancer (BC) is a common malignant tumour for the adult female and its relative incidence has increased continuously in recent years. The primary molecular mechanisms of breast tumourigenesis remain unclear. With the sequencing technology, we found that coatomer protein complex subunit beta 2 (COPB2) gene is overexpressed in breast cancer tissues. However, the biological function of COPB2 in BC has yet to be determined. This current research demonstrates, significant up-regulation of COPB2 in tissues of breast cancer while comparing the adjacent normal tissue both invalidated cohort and TCGA cohort. Up-regulated expression of COPB2 was correlated with lymph node metastasis (LNM) and oestrogen receptor (ER) in the TCGA cohort and a high level of COPB2 was associated with age and lymph node metastasis in the validated cohort. Besides, logistic analysis illustrated in BC patient COPB2 expression, tumour size, age, ER and disease stage were independent high-risk factors of LNM. Loss of function experiments revealed that down-regulation of COPB2 could inhibit capacities of proliferation and cell invasion in MDA-MB-231 and BT-549 cell lines. Moreover, underexpression of COPB2 could decrease the EMT-related protein N-cadherin and vimentin which may lead to cell invasion. This current research provides new shreds of evidence that COPB2 overexpression shows significant character in the progression of breast cancer. To best of our knowledge, our findings indicated that COPB2 was vital oncogene which was associated with breast cancer.

Growth-associated protein 43 promotes thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next-generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up-regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC-1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial-mesenchymal transition-related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.

Protective effects of maresin 1 against inflammation in experimentally induced acute pancreatitis and related lung injury.

Severe acute pancreatitis (SAP) is an inflammatory disorder that progresses with local and systemic difficulties accompanied by a relatively high mortality rate. In recent years, maresin 1 (MaR1) has been shown to be a macrophage mediator with effective proresolving and anti-inflammatory properties that prevents the occurrence of various inflammatory conditions. The purpose of this study was to investigate the role of MaR1 in SAP and related lung injury. Experimental SAP was induced in mice with a combination of cerulean and lipopolysaccharide. MaR1 was administered 30 min before the primary injection of cerulean. Biochemical markers and histological injury scores were used to evaluate the severity of acute pancreatitis. To determine the degree of inflammation, serum cytokines and myeloperoxidase activity in pancreas and lung tissues were measured. Western blot analysis detected the activation of NF-κB. After MaR1 pretreatment, the activities of amylase, lipase, TNF-α, IL-1ß, and IL-6 were decreased in serum, and the myeloperoxidase activity both in pancreas and in lung tissues significantly decreased, whereas the activity of anti-inflammatory cytokine IL-10 in serum was increased. MaR1-pretreated mice reduced the activation of pancreatic NF-κB and decreased the severity of pancreatic and lung-related injuries. These results confirm that MaR1 alleviated inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimentally induced acute pancreatitis and exerted anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of SAP.NEW & NOTEWORTHY These results provided us evidence to confirm that maresin 1 (MaR1) can alleviate inflammation of the pancreas and lung by inhibiting the activity of NF-κB in experimental induced acute pancreatitis and exerts certain anti-inflammatory effects. These findings suggest that MaR1 could be a new and useful drug in the treatment of severe acute pancreatitis.

IGSF1: A novel oncogene regulates the thyroid cancer progression.

Thyroid cancer has been continuously increasing and extraordinarily prevalent worldwide. The genetic diagnosis has been widely used in fine needle aspiration. IGSF1, an immunoglobulin superfamily member 1, has been shown to be associated with the regulation of thyroid hormone. But the function of IGSF1 in thyroid cancer has not been explored yet. In this article, we will illuminate the correlation between IGSF1 expression and thyroid cancer. We analysed the level of IGSF1 expression in 55 pairs of tissue samples by real-time polymerase chain reaction (PCR) and The Cancer Genome Atlas (TCGA) data portal. After that, we transfected small interfering RNA to silence IGSF1 in thyroid cancer cell lines (KTC-1 and BCPAP) and confirmed the function of IGSF1 by performed colony formation, migration, invasion, cell counting kit-8, and apoptosis assays. IGSF1 was upregulated in thyroid cancer tissues compared with the adjacent normal tissues (t = 5.783, df = 54; P < .0001) and TCGA (T: N = 65.91 ± 3.998, n = 501: 2.824 ± 0.273, n = 58; P < .0001). In thyroid cell lines, experiments showed that downregulated IGSF1 inhibited proliferation, metastasis, and promoted cell apoptosis. Meanwhile, inhibited IGSF1 expression could downregulate N-cadherin, vimentin, and EZH2, which is associated with metastasis. Thyroid cancer cells IGSF1 expression levels are a correlation with its ability to growth, metastasis, and apoptosis.

lncRNA FOXD3-AS1 is associated with clinical progression and regulates cell migration and invasion in breast cancer.

For women, breast cancer is the most commonly diagnosed cancer and the leading cause of women deaths due to cancer. In recent years, increasing long noncoding RNA (lncRNA) has been discovered to be related to tumorigenesis, progression, and prognosis. FOXD3-AS1 is a lncRNA and has been identified as a cancer-promoting gene in glioma. By analysing the FOXD3-AS1 expression in The Cancer Genome Atlas (TCGA) database, we found that FOXD3-AS1 has significantly high expression in breast cancer tumour comparing with the normal tissue. And patients with low FOXD3-AS1 expression had greater survival probability, smaller tumour size, and less distant metastasis. This leads us to peep inquisitively biological function of FOXD3-AS1 in breast cancer. Biological assays demonstrated that silenced FOXD3-AS1 impaired cell proliferation and inhibited cell migration and invasion in breast cancer cell lines (BT549, MDA-MB-231). These results suggest that FOXD3-AS1 could play a potential diagnostics or prognostic biomarker for patients with breast cancer. SIGNIFICANCE OF THE STUDY: We demonstrated that lncRNA FOXD3-AS1 has significantly high expression in breast cancer cell lines comparing with the normal tissue. Besides, our findings suggested that lncRNA FOXD3-AS1 could play a potential diagnostics or prognostic biomarker for patients with breast cancer.

MAL2 promotes proliferation, migration, and invasion through regulating epithelial-mesenchymal transition in breast cancer cell lines.

BACKGROUND: Breast cancer is one of the most common malignant tumors in women. However, the underlying molecular mechanisms of breast cancer are still far to clear. With the development of sequencing technology, we discovered that MAL2 is overexpressed in tumor tissues. But the major function of MAL2 in breast cancer has not to be well confirmed. MATERIALS AND METHODS: We downloaded and analyzed the MAL2 expression in The Cancer Genome Atlas (TCGA) database. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to detect the expression of MAL2 in 35 breast cancer patients. Then, we performed proliferation, colony formation, migration, invasion and western blot assays to investigate the role of MAL2 in breast cancer cell lines (MDA-MB-231 and BT-549). RESULTS: In our research, we found that MAL2 is remarkably overexpressed in breast cancer tissues compared to adjacent non-cancer tissues by RT-qPCR (T: N = 5.28 ±â€¯4.34:1.82 ±â€¯1.11, P < 0.001) and high expression of MAL2 has worse overall survival in TCGA cohort (P = 0.0032). Knocked down MAL2 could decrease the ability of proliferation, migration, and invasion of breast cancer cell lines. Our Western Blot assay results investigated that MAL2 could regulate EMT. CONCLUSION: In this study, we demonstrated the function of MAL2 in breast cancer cell lines and it might act as an oncogene in breast cancer.

LRP4 promotes proliferation, migration, and invasion in papillary thyroid cancer.

Dysregulation of cell proliferation and death is considered the foundation of the malignant biological characteristics of cancer. In this study, we conducted a comprehensive analysis of a massively parallel whole transcriptome resequencing of paired papillary thyroid cancer and normal thyroid tissues from 19 patients. In addition, we found that LRP4, a member of the low-density lipoprotein receptor-related protein family, is significantly overexpressed in thyroid carcinoma. We demonstrated through quantitative real-time polymerase chain reaction (qRT-PCR) that LRP4 is upregulated in papillary thyroid cancer (PTC) tissues. This observation was also consistent with data analyzed from The Cancer Genome Atlas (TCGA) cohort. Thus, the biological role of LRP4 in the thyroid cancer in the present study was investigated using the PTC cell lines TPC1, BCPAP and KTC-1. In these cell lines, the mRNA level of LRP4 was higher than normal thyroid cancer cell named HTORI3. In vitro experiments demonstrated that LRP4 downregulation significantly inhibited the colony formation, proliferation, migration, and invasion of the three PTC cell lines. Knockdown of LRP4 by small interfering RNA (siRNA) in those cell lines decreased the protein expression of N-cadherin, Enhancer of zeste homolog 2 (EZH2), and Zinc finger E-box-binding home-box 1 (ZEB1). Furthermore, LRP4 knockdown significantly reduced the levels of phosphorylated PI3K in the PTC cell lines. In conclusion, the present study indicated that LRP4 is a gene associated with PTC and might become a potential therapeutic target.

LncRNA CCND2-AS1 promotes proliferation, migration, and invasion in papillary thyroid carcinoma.

In decades, a lot of long non-coding RNAs (LncRNAs) have been proven to exert influences on tumorigenesis in vitro and in vivo. Many lncRNAs have been reported as effective therapeutic targets and biomarkers in various cancers. However, whether LncRNAs are associated with the progression of PTC remains largely unknown. In this study, we measured the expression of CCND2-AS1 in PTC cell lines by quantitative real-time polymerase chain reaction (qRT-PCR).We found that CCND2-AS1 expression was significantly over-expressed in PTC cell lines compared to normal thyroid epithelial cells. Gain-and loss-of-function experiments were performed to investigate the role of CCND2-AS1 in PTC cells. In vitro experiments, we proved that CCND2-AS1 knockdown in TPC1 significantly suppressed cell proliferation, migration, and invasion, while CCND2-AS1 overexpression in BCPAP had the opposite effects. Meanwhile, we also found that CCND2-AS1 could regulate N-cadherin and Vimentin expression, which may influence invasion and migration. Our findings indicate that the lncRNA CCND2-AS1 is a gene associated with PTC and might become a potential therapeutic target.

Dihydroartemisinin potentiates antitumor activity of 5-fluorouracil against a resistant colorectal cancer cell line.

Although the combination of chemotherapy and surgical resection has effectively increased the survival rate of colorectal cancer patients in recent decades, acquired drug resistance is still a problem that leads to treatment failure. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently been reported to show anticancer effects against numerous types of cancer, including colorectal cancer. This study showed that DHA exerted a strong anticancer effect against several colorectal cancer cell lines. We also found that p53 knockout colorectal cancer HCT116 cells (HCT116 TP53-/-) were not sensitive to 5-fluorouracil (5-FU) treatment, unlike wild-type HCT116 cells. Interestingly, co-treatment with DHA could effectively restore the anticancer effect of 5-FU against HCT116 TP53-/- cells, which manifested as the inhibition of proliferation and induction of reactive oxygen species (ROS)-mediated apoptosis and was accompanied by the upregulation of B-cell lymphoma 2 (BCL-2) and downregulation of the BCL-2-associated X protein (BAX). These findings suggested that DHA could effectively sensitize cells to 5-FU through ROS-mediated apoptosis and the alteration of the BCL-2/BAX expression ratio, which indicated that this may be one of the mechanisms of the DHA-promoted 5-FU anticancer effect.

A novel long non-coding RNA FGF14-AS2 is correlated with progression and prognosis in breast cancer.

Breast cancer is diverse in their natural history and in their responsiveness to treatments. It is urgent to generate candidate biomarkers for the stratification of patients and personalization of therapy to avoid overtreatment or inadequate treatment. Long noncoding RNAs (lncRNAs) have been found to be pervasively transcribed in the genome and played critical roles in cancer progression. A lot of lncRNAs have been reported as potential prognostic biomarkers and therapeutic targets in multiple cancers. In this study, we demonstrated that FGF14 antisense RNA 2 (FGF14-AS2), a novel long non-coding RNA, was significantly down-regulated in breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Reduced expression of FGF14-AS2 was correlated with larger tumor size, more lymph node metastasis and advanced clinical stage in both cohorts. Kaplan-Meier analysis indicated that patients with lower FGF14-AS2 expression had a worse overall survival. Moreover, multivariate analysis revealed that decreased expression of FGF14-AS2 was an independent predictor of overall survival. Together, these results suggested that FGF14-AS2 involved in the progress of breast cancer and might act as a tumor suppressor gene. To the best of our knowledge, it was firstly reported that FGF14-AS2 was involved in cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment.

Exploring the Oncogenic Potential of TIMM8A: A Crucial Factor in Breast Cancer Tumorigenesis.

BACKGROUND: Female breast cancer has become the world's most common malignant tumor, displacing lung malignancy, and the incidence of malignant tumors has increased continuously in recent decades. However, the underlying molecular mechanisms of breast tumorigenesis have not been fully elucidated. By consulting the literature, we discovered that the TIMM8A gene could affect oxidative stress and apoptosis in patients with Mohr-Tranebjærg syndrome. However, the biological function of TIMM8A has yet to be explored. MATERIALS AND METHODS: We investigated the expression level of TIMM8A via bioinformatic analysis and performed immunohistochemistry, diagnostic value, immune infiltration, functional enrichment, and survival analyses. Nonetheless, in vitro, additional experiments were performed. We explored whether TIMM8A expression was greater in breast tumors than in nearby normal tissues through qRT‒PCR. The expression of TIMM8A was knocked down by siRNA. Then, we conducted proliferation tests (CCK-8 experiment and colony formation) and Transwell assays (migration and invasion assays) to determine the specific biological functions of TIMM8A in the MDA-MB-231 and BT-549 cell lines. RESULTS: Tumor samples exhibited higher TIMM8A expression and exon expression, whereas normal tissues had higher TIMM8A methylation. The expression level of TIMM8A was linked to immune infiltration and survival, making it a valuable prognostic indicator and effective diagnostic tool. Functional enrichment analysis of TIMM8A indicated potential pathways through which it may play a role. In vitro experiments demonstrated that suppressing TIMM8A significantly inhibited the viability, colony formation, migration, and invasion of breast carcinoma cell lines. CONCLUSION: This study revealed that TIMM8A is an oncogene and is critical for the tumorigenesis of breast carcinoma.