TP73-AS1 as a predictor of clinicopathological parameters and prognosis in human malignancies: a meta and bioinformatics analysis.

BACKGROUND: Long non-coding RNA P73 antisense RNA 1 T (non-protein coding), also known as Lnc RNA TP73-AS1, is dysregulated in various tumors but the correlation between its expression and clinicopathological parameters and/or prognoses in cancer patients is inconclusive. Here, we performed a meta-analysis to evaluate the prognostic value of Lnc RNA TP73-AS1 for malignancies. METHODS: We systematically searched four online databases including PubMed, the Web of Science, Embase, and the Cochrane Library for eligible articles published up to June 29/2020. Odds ratios (ORs) and Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the association of TP73-AS1 expression with prognostic and clinicopathological parameters. We further validated TP73-AS1 expression in various malignancies and its potential prognostic value using the GEPIA online database. We predicted potential biological processes and relevant signal mechanisms through the public databases. RESULTS: A total of 26 studies examining 14 cancers were analyzed to evaluate the relationship between TP73-AS1 expression, clinicopathological features and prognostic indicators. The results indicated that TP73-AS1 expression markedly correlates with TNM stage (OR = 3.27,95% CI:2.43-4.39, P < 0.00001), tumor size (OR = 3.00, 95%CI:2.08-4.35, P < 0.00001), lymph node metastasis (OR = 2.77, 95%CI:1.42-5.38,P < 0.00001) and distant metastasis (OR = 4.50,95%CI:2. 62-7.73,P < 0.00001). No correlation with age (OR = 1.12,95%CI:0.77-1.64, P > 0.05), gender (OR = 1.08, 95%CI:0.84-1.38, P > 0.05) or differentiation (OR = 1.39, 95%CI:0.71-2.70, P = 0.340) was observed. TP73-AS1 overexpression was a biomarker of poor Overall survival(OS)(HR = 1.85,95%CI:1.53-2.22, P < 0.00001) and Disease-Free-Survival (DFS) (HR = 1.57,95%CI:1.03-2.42, P < 0.05). Dysregulated TP73-AS1 expression and its prognostic value in various cancers was validated based on The Cancer Genome Atlas (TCGA). Further biological function predictions indicated that TP73-AS1 was involved in pro-oncogenic signaling. CONCLUSIONS: The upregulation of Lnc RNA TP73-AS1 was related to detrimental clinicopathological parameters and can be considered an indicator of poor prognosis for cancer malignancies.

Long non-coding RNA SNHG15 in various cancers: a meta and bioinformatic analysis.

BACKGROUND: The snoRNA host gene SNHG15 produces a long non-coding RNA (lncRNA) with a short half-life and has been reported to be dysregulated in multiple cancers and has recently been found to be correlated with tumour progression. Therefore, this meta-analysis was performed to evaluate the generalised prognostic role of small nucleolar RNA host gene 15 (SNHG15) in malignancies, based on variable data from different studies. METHODS: Four public databases were used to identify eligible studies. The association between prognostic indicators and clinical features was extracted and pooled to estimate the hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was measured using Begg's test and Egger's test, and the stability of pooled results were measured using sensitivity analysis. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was screened to further validate our results. Ultimately, we predicted the molecular regulation of SNHG15 based on the public databases. RESULTS: In total, 11 studies including 1087 patients were ultimately enrolled in our meta-analysis. We found that SNHG15 overexpression was associated with worse overall survival (OS) and disease-free survival (DFS), and this was validated in the Gene Expression Profiling Interactive Analysis (GEPIA) cohort. Moreover, increased SNHG15 expression suggested advanced TNM stage and LNM, but was not associated with age, gender, or tumour size. No publication bias or instability of the results was observed. SNHG15 was significantly upregulated in seven cancers and elevated expression of SNHG15 indicated shorter OS and DFS in five malignancies based on the validation using the GEPIA cohort. Further functional prediction indicated that SNHG15 may participate in some cancer-related pathways. CONCLUSIONS: Upregulation of lncRNA SNHG15 was notably associated with worse prognosis and clinical features, suggesting that SNHG15 might serve as a novel prognostic factor in various cancers.

Antiangiogenic therapy for Wilms tumor in an adult and literature review.

Wilms tumor is extremely rare in adults. There is no standard treatment for Wilms tumor in adults, and the therapy protocols are based on those used in children. Here, we report a case of Wilms tumor in a 24-year-old woman who was effectively treated with apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2. The favorable outcome suggested that antiangiogenic therapy might be effective in treating adults with Wilms tumors. Starting with this case, we reviewed the features of Wilms tumors in adults and its treatment with antiangiogenic therapy. The information in this review could provide a novel approach to treating adults with Wilms tumors.

SH3BP1-induced Rac-Wave2 pathway activation regulates cervical cancer cell migration, invasion, and chemoresistance to cisplatin.

Cervical cancer still remains the fourth most common cancer, affecting women worldwide with large geographic variations in cervical cancer incidence and mortality rates. SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target Wave2 is required for cell motility, thus regarded as an essential regulator of cancer cell metastasis. However, the exact effects and molecular mechanisms of SH3BP1 in cervical cancer progression are still unknown. The present study is aimed to investigate the mechanism of SH3BP1 in regulation of cervical cancer cell metastasis and chemoresistance. In the present study, we demonstrated a high SH3BP1 expression in cervical cancer tissues; a higher SH3BP1 expression is also correlated with a shorter overall survival of patients with cervical cancer. Further, we revealed that SH3BP1 overexpression promoted the invasion, migration, and chemoresistance of cervical cancer cell through increasing Rac1 activity and Wave2 protein level. The promotive effect of SH3BP1 could be partially reversed by a Rac1 inhibitor, NSC 23766. In cisplatin-resistant cervical cancer tissues, SH3BP1, Rac1, and Wave2 mRNA expression was significantly up-regulated compared to that of the cisplatin-sensitive cervical cancer tissues. Taken together, SH3BP1/Rac1/Wave2 pathway may potentially act as an effective therapeutic target combined with traditional cisplatin-based chemotherapy for cervical cancer.

Using Artificial Intelligence (Watson for Oncology) for Treatment Recommendations Amongst Chinese Patients with Lung Cancer: Feasibility Study.

BACKGROUND: Artificial intelligence (AI) is developing quickly in the medical field and can benefit both medical staff and patients. The clinical decision support system Watson for Oncology (WFO) is an outstanding representative AI in the medical field, and it can provide to cancer patients prompt treatment recommendations comparable with ones made by expert oncologists. WFO is increasingly being used in China, but limited reports on whether WFO is suitable for Chinese patients, especially patients with lung cancer, exist. Here, we report a retrospective study based on the consistency between the lung cancer treatment recommendations made for the same patient by WFO and by the multidisciplinary team at our center. OBJECTIVE: The aim of this study was to explore the feasibility of using WFO for lung cancer cases in China and to ascertain ways to make WFO more suitable for Chinese patients with lung cancer. METHODS: We selected all lung cancer patients who were hospitalized and received antitumor treatment for the first time at the Second Xiangya Hospital Cancer Center from September to December 2017 (N=182). WFO made treatment recommendations for all supported cases (n=149). If the actual therapeutic regimen (administered by our multidisciplinary team) was recommended or for consideration according to WFO, we defined the recommendations as consistent; if the actual therapeutic regimen was not recommended by WFO or if WFO did not provide the same treatment option, we defined the recommendations as inconsistent. Blinded second round reviews were performed by our multidisciplinary team to reassess the incongruent cases. RESULTS: WFO did not support 18.1% (33/182) of recommendations among all cases. Of the 149 supported cases, 65.8% (98/149) received recommendations that were consistent with the recommendations of our team. Logistic regression analysis showed that pathological type and staging had significant effects on consistency (P=.004, odds ratio [OR] 0.09, 95% CI 0.02-0.45 and P<.001, OR 9.5, 95% CI 3.4-26.1, respectively). Age, gender, and presence of epidermal growth factor receptor gene mutations had no effect on consistency. In 82% (42/51) of the inconsistent cases, our team administered two China-specific treatments, which were different from the recommendations made by WFO but led to excellent outcomes. CONCLUSIONS: In China, most of the treatment recommendations of WFO are consistent with the recommendations of the expert group, although a relatively high proportion of cases are still not supported by WFO. Therefore, WFO cannot currently replace oncologists. WFO can improve the efficiency of clinical work by providing assistance to doctors, but it needs to learn the regional characteristics of patients to improve its assistive ability.

Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin.

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the roles and regulatory mechanisms of the novel lncRNA, cancer susceptibility candidate 2 (CASC2), in cervical cancer tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in cervical cancer tissues, and was related to a shorter survival time and poorer clinicopathologic features. Exogenous CACS2 alone was sufficient to inhibit cervical cancer cell proliferation and amplified DDP-induced repression of cell proliferation. A lower expression of CACS2 was observed in the DDP-resistant cervical cancer tissues, compared to DDP-sensitive cancer tissues; CACS2 overexpression could sensitize DDP-resistant cervical cancer cell (HeLa/DDP and CaSki/DDP) to DDP. Further functional experiments indicate that CASC2 upregulated PTEN expression by direct inhibiting miR-21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AKT protein. In DDP-resistant cervical cancer tissues, miR-21 was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays an important role in cervical cancer sensitivity to DDP and may serve as a potential target for cancer diagnosis and treatment.

Oncogenic roles and drug target of CXCR4/CXCL12 axis in lung cancer and cancer stem cell.

Although the great progress has been made in diagnosis and therapeutic in lung cancer, it induces the most cancer death worldwide in both males and females. Chemokines, which have chemotactic abilities, contain up to 50 family members. By binding to G protein-coupled receptors (GPCR), holding seven-transmembrane domain, they function in immune cell trafficking and regulation of cell proliferation, differentiation, activation, and migration, homing under both physiologic and pathologic conditions. The alpha-chemokine receptor CXCR4 for the alpha-chemokine stromal cell-derived-factor-1 (SDF-1) is most widely expressed by tumors. In addition to human tissues of the bone marrow, liver, adrenal glands, and brain, the CXC chemokine SDF-1 or CXCL12 is also highly expressed in lung cancer tissues and is associated with lung metastasis. Lung cancer cells have the capabilities to utilize and manipulate the CXCL12/CXCR system to benefit growth and distant spread. CXCL12/CXCR4 axis is a major culprit for lung cancer and has a crucial role in lung cancer initiation and progression by activating cancer stem cell. This review provides an evaluation of CXCL12/CXCR4 as the potential therapeutic target for lung cancers; it also focuses on the synergistic effects of inhibition of CXCL12/CXCR4 axis and immunotherapy as well as chemotherapy. Together, CXCL12/CXCR4 axis can be a potential therapeutic target for lung cancers and has additive effects with immunotherapy.

Nuclear factor-κB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog.

Nuclear factor-κB (NF-κB) may activate a series of gene transcription control cellular signaling pathways whose products are components in a wide range of biological processes. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Using human cervical cancer cell lines, we explored whether NF-κB regulates the expression of microRNA-130a (miR-130a) through binding elements in the miR-130a promoter region. We found that miR-130a accelerates cervical cancer cell proliferation by targeting the phosphatase and tensin homolog on chromosome 10 (PTEN). Further, NF-κB activates both HeLa and CaSki cell growth by upregulating miR-130a. In addition, by targeting PTEN 3' untranslated region, miR-130a might increase cell growth and initiate protein kinase B (AKT) pathway activation. Lastly, PTEN protein was upregulated in response to NF-κB overexpression and downregulated in response to NF-κB inhibition. Compared to total AKT protein level, p-AKT was downregulated by NF-κB overexpression while upregulated by NF-κB inhibition, indicating PTEN pathway activated and affected by NF-κB. Taken together, our findings shed new light on the NF-κB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the carcinogenesis of cervical cancer.

Propensity score matching analysis to comparing cisplatin versus nedaplatin based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer.

This study evaluated the efficacy and safety of cisplatin and nedaplatin in three-week doublet agent concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC). We retrospectively enrolled patients with stage IIB-IIIC2 cervical cancer who received doublet agent CCRT from January 2015 to December 2020. Clinical outcomes were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Propensity score (PS) matching analysis was used to compare cisplatin plus docetaxel group and nedaplatin plus docetaxel group. A total of 295 patients were included. The 5-year overall survival rate (OS) and progression free survival rate (PFS) were 82.5% and 80.4%, respectively. After PS matching, there were 83 patients each in the nedaplatin group and cisplatin group. There were no significant differences in objective response rates (97.6% and 98.8%, p = 0.212), 5-year OS rate (96.5 vs 69.8, p = 0.066), PFS rate (90.8 vs 72.4, p = 0.166), and toxicity between the two groups. Doublet agent concurrent chemoradiotherapy is feasible, safe, and shows high efficacy in LACC patients. Here, cisplatin group has a trend of better prognosis, suggesting that cisplatin is preferred and nedaplatin can be considered for replacement when cisplatin is intolerant.

Real-world retrospective study of immune checkpoint inhibitors in combination with radiotherapy or chemoradiotherapy as a bladder-sparing treatment strategy for muscle-invasive bladder urothelial cancer.

Background: Recent developments in MIBC treatment suggest good efficacy of bladder sparing treatment combined with immune checkpoint inhibitor. However, there is no standard treatment mode. A retrospective analysis was conducted to reveal the efficacy and safety of PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy. Methods: We retrospectively analyzed 25 patients with MIBC T2-T3N0M0 disease who were unfit or unwilling to undergo RC. These patients underwent the maximum TURBT followed by PD-1 inhibitor (Tislelizumab or Toripalimab) in combination with radiotherapy or chemoradiotherapy (gemcitabine plus cisplatin) between April 2020 and May 2022. The primary outcome was clinical complete response (cCR) rate. The secondary outcomes were disease free survival (DFS) and overall survival (OS). Results: Revised: Of 25 patients, 22 were T2 (88%), while 3 were T3 (12%). The median age is 65 years (51-80). Twenty-one patients had programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or more, and 4 patients had CPS<1 or unknown. Sixteen patients received chemoradiotherapy. Tislelizumab and Toripalimab were administered to 19 and 6 patients, respectively. The median number of cycles of immunotherapy was 8. Twenty-three patients (92%) achieved cCR. Following a median of 13 months of follow-up (range, 5-34 months), 1-year DFS and OS rate were 92% and 96%, respectively. In the univariate analysis, T stage significantly influenced OS and ORR, and efficacy evaluation significantly influenced OS, DFS, and ORR. The expression of PD-L1 and chemotherapy had no effect on prognosis. In the multivariate analysis, no independent prognostic factors were found. Grade 3 or 4 adverse events (AE) were reported in 35.7% patients. Conclusions: Bladder sparing therapy with PD-1 inhibitor in combination with radiotherapy or chemoradiotherapy is feasible, safe, and highly effective for patients who were unfit or unwilling to undergo RC.

The Research Landscape of Multiple Endocrine Neoplasia Type 1 (2000-2021): A Bibliometric Analysis.

Introduction: This study aimed to investigate the landscape of Multiple Endocrine Neoplasia Type 1 research during the last 22 years using machine learning and text analysis. Method: In December 2021, all publications indexed under the MeSH term "Multiple Endocrine Neoplasia Type 1" were obtained from PubMed. The whole set of search results was downloaded in XML format, and metadata such as title, abstract, keywords, mesh words, and year of publication were extracted from the original XML files for bibliometric evaluation. The Latent Dirichlet allocation (LDA) topic modeling method was used to analyze specific themes. Results: This study eventually contained 1,407 publications. Among them, there are 768 (54.58%) case reports and reviews. Text analysis based on MeSH words revealed that the most often studied clinical areas include therapy efficacy, prognosis, and genetic diagnosis. The majority of basic study is focused on genetic alterations. The LDA topic model further identifies three topic clusters include basic research, treatment cluster, and diagnosis cluster. In the basic research cluster, many studies are focused on the expression of Menin. The primary focus of the therapy cluster is pancreatic resections and parathyroidectomy. In the diagnose cluster, the main focus is on Genetic Diagnosis and screening strategies for Hereditary Cancer Syndrome. Conclusion: The current state of research on MEN1 is far from adequate. Research on rare diseases MEN1 necessitates implementing a broad research program involving multiple centers to advance MEN1 research together.

Trends in Worldwide Research in Inflammatory Bowel Disease Over the Period 2012-2021: A Bibliometric Study.

Background: Inflammatory bowel disease (IBD) is a continuously increasing and worldwide disease, and the number of publications of IBD has been expanding in the past 10 years. The purpose of this study is to analyze the published articles of IBD in the past decade via machine learning and text analysis and get a more comprehensive understanding of the research trends and changes in IBD in the past 10 years. Method: In November 2021, we downloaded the published articles related to IBD in PubMed for the past 10 years (2012-2021). We utilized Python to extract the title, publication date, MeSH terms, and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet allocation (LDA) was used to the abstracts to identify publications' research topics with greater specificity. Result: We finally identified and analyzed 34,458 publications in total. We found that publications in the last 10 years were mainly focused on treatment and mechanism. Among them, publications on biological agents and Gastrointestinal Microbiome have a significant advantage in terms of volume and rate of publications. In addition, publications related to IBD and coronavirus disease 2019 (COVID-19) have increased sharply since the outbreak of the worldwide pandemic caused by novel ß-coronavirus in 2019. However, researchers seem to pay less attention to the nutritional and psychological status of patients with IBD. Conclusion: IBD is still a worldwide disease of concern with the publication of IBD-related research has expanded continuously over the past decade. More research related nutritional and psychological status of patients with IBD is needed in the future. Besides, it is worth noting that the management of chronic diseases such as IBD required additional attention during an infectious disease epidemic.

Exploring the research landscape of the past, present, and future of thyroid nodules.

Introduction: The purpose of this study was to assess the landscape of thyroid nodules research during the last 22 years using machine learning and text analysis. Methods: In November 2021, we obtained from PubMed all works indexed under the Medical Subject Headings (MeSH) subject line "thyroid nodules." The entire set of search results was retrieved in XML format, and metadata such as title, abstract, keywords, MeSH words, and year of publication were extracted for bibliometric evaluation from the original XML files. To increase the specificity of the investigation, the Latent Dirichlet allocation (LDA) topic modeling method was applied. Results: Our study included 5,770 research papers. By using frequency analysis of MeSH terms, research on thyroid nodules was divided into two categories: clinical and basic. The proportion of clinical research is nearing 89% and is dominated by the differential diagnosis of thyroid nodules. In contrast, the proportion of MeSH terms relating to basic research was just 11%, with DNA mutation analysis being the most common topic. Following this, LDA analysis revealed the thyroid nodule study had three clusters: Imaging Studies, Biopsy and Diagnosis, and Epidemiology and Screening of Thyroid Cancer. The result suggests that current thyroid nodule research appears to have focused on ultrasonography and histological diagnosis, which are tightly correlated. Molecular biomarker research has increased, therefore enhancing the diagnostic precision of thyroid nodules. However, inflammation, anxiety, and mental health disorders related to thyroid nodules have received little attention. Conclusion: Basic research on thyroid nodules has unmet research requirements. Future research could focus on developing strategies to more efficiently identify malignant nodules, exploring the mechanism of thyroid nodule development, and enhancing the quality of life of thyroid patients.

A Bibliometric Analysis of the Landscape of Parathyroid Carcinoma Research Based on the PubMed (2000-2021).

INTRODUCTION: The purpose of this study was to assess the landscape of parathyroid carcinoma research during the last 22 years using machine learning and text analysis. METHOD: In November 2021, we obtained from PubMed all works indexed under the mesh subject line "parathyroid carcinoma". The entire set of search results was retrieved in XML format, and metadata such as title, abstract, keywords, mesh words, and year of publication were extracted for bibliometric evaluation from the original XML files. To increase the specificity of the investigation, the Latent Dirichlet allocation (LDA) topic modeling method was applied. RESULTS: The paper analyzed 3578 papers. The volume of literature related to parathyroid cancer has been relatively flat over the past 22 years. In the field of parathyroid cancer research, the most important topic of clinical interest is the differential diagnosis. Ultrasound and MIBI are the most commonly used imaging methods for localization. In terms of basic research, the mechanisms of gene mutation and local tumor recurrence are the focus of interest. CONCLUSION: There are huge unmet research needs for parathyroid carcinoma. Improving the diagnosis rates of parathyroid cancer by clinicians and establishing new and reliable molecular pathological markers and new image localization techniques will continue to be the focus of future research.

Clinicopathological Significance of ATRX Expression in Nasopharyngeal Carcinoma Patients: A Retrospective Study.

Background: Nasopharyngeal carcinoma (NPC) is the most common head and neck squamous cell carcinoma in south China. Radiation technology improves the local control rates in early NPC. However, the distant metastases are still the main cause of treatment failure. Thus, to find biomarkers for prognosis will help to enhance the survival of NPC. ATRX is a chromatin remodeling protein localized in the nucleus. Deletion or mutation of ATRX gene has been demonstrated in a variety of malignancies. However, the significance of ATRX expression in the prognosis of NPC remains unclear. Methods: Tumor tissues from 227 NPC patients diagnosed in the Second Xiangya Hospital of Central South University from 2011 to 2016 were selected. Immunohistochemistry was used to detect the ATRX expression level of the tumor tissue. Chi-square test was used to analyze the relationship between ATRX expression and clinical characteristics such as age, sex, T stage, N stage and clinical stage. Kaplan-Meier method was used for survival analysis, and log-rank was used to compare the difference in survival rate. Results: There were 53 patients with negative ATRX expression, accounting for 24.2% of the total group. ATRX expression was not significantly associated with age, sex, N stage, clinical stage, and progression-free survival (PFS) (P>0.05). However, patients with negative ATRX expression had earlier T staging (P=0.045) and a higher 5-year overall survival (84.9% vs 66.9%, P=0.022). Conclusions: Loss of ATRX expression may contribute to better prognosis in patients with NPC.

The Role of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 Regulatory Loop in Cervical Cancer Cell Growth and Resistance to Cisplatin.

Cervical cancer is a highly prevalent female malignancy. Presently, cisplatin (DDP) is a first-line agent for cervical cancer chemotherapy. However, its curative effect is limited because of chemo-resistance. It has been previously reported that SOX9 targeted and activated oncogenic genes, enhancing cervical cancer cell resistance to DDP. The effects of the SOX9/lncRNA ANXA2P2/miR-361-3p/SOX9 regulatory loop on cervical cancer cell growth and resistance to DDP have been demonstrated. miR-361-3p expression was decreased in DDP-resistant cervical cancer cells and tissues. Moreover, miR-361-3p overexpression inhibited the growth of resistant cervical cancer cells and the resistance to DDP, whereas miR-361-3p inhibition exerted opposite effects. miR-361-3p inhibited SOX9 expression through binding; the effects of miR-361-3p inhibition were partially reversed by SOX9 knockdown. LncRNA ANXA2P2 expression was elevated in DDP-resistant cervical cancer cells and tissues. LncRNA ANXA2P2 inhibited miR-361-3p expression by binding, thereby upregulating SOX9. LncRNA ANXA2P2 knockdown inhibited DDP-resistant cervical cancer cell growth and resistance to DDP, whereas the effects of lncRNA ANXA2P2 knockdown were partially reversed by miR-361-3p inhibition. SOX9 expression was elevated in DDP-resistant cervical cancer cells and tissues, and SOX9 activated lncRNA ANXA2P2 transcription by binding. Collectively, SOX9, lncRNA ANXA2P2, and miR-361-3p form a regulatory loop, modulating DDP-resistant cervical cancer cell growth and response to DDP treatment.

Corrigendum: Alpha Thalassemia/Intellectual Disability X-Linked Deficiency Sensitizes Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.

[This corrects the article DOI: 10.3389/fonc.2020.608300.].

Long non­coding RNA SNHG1 promotes breast cancer progression by regulation of LMO4.

Long non­coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) was reported to be a critical regulator of tumorigenesis and is frequently deregulated in several cancer types. However, the exact mechanism by which SNHG1 contributes to breast cancer progression has not been fully elucidated. The identification of the molecular mechanism of SNHG1 is important for understanding the development of breast cancer and for improving the prognosis of the patients with this disease. In the present study, increased expression levels of SNHG1 were noted in breast cancer tumors following analysis of differentially expressed lncRNAs between 1,063 tumor and 102 normal tissues derived from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA­BRCA) dataset. This finding was further validated using 50 pairs of normal and tumor tissues that were collected from patients with breast cancer. Notably, SNHG1 expression was significantly correlated with estrogen receptor (ER)/progesterone receptor (PR) negative status (ER­/PR­) and advanced clinical stage in breast cancer tissues. Knockdown of SNHG1 led to cell growth arrest, cell cycle redistribution and cell migration inhibition of breast cancer cells. The miRDB database predicted that miR­573 interacts with SNHG1. RT­PCR confirmed the negative regulation of miR­573 levels by SNHG1 in breast cancer cells and the Dual­luciferase reporter assay confirmed their complementary binding. The repression of miR­573 by SNGH1 decreased LIM domain only 4 (LMO4) mRNA and protein expression levels in the breast cancer cell lines tested and induced the expression of cyclin D1 and cyclin E. In vitro experiments indicated that LMO4 overexpression could reverse siSNHG1­induced cell growth arrest, cell cycle redistribution and inhibition of cell migration in breast cancer cells. Moreover, the tumor xenograft model indicated that SNHG1 knockdown inhibited MDA­MB­231 growth in vivo and LMO4 overexpression reversed the tumor growth inhibition induced by SNHG1 knockdown. The present study demonstrated that SNHG1 acts as a novel oncogene in breast cancer via the SNHG/miR­573/LMO4 axis and that it could be a promising therapeutic target for patients with breast cancer.

Alpha Thalassemia/Intellectual Disability X-Linked Deficiency Sensitizes Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.

BACKGROUND: The immune checkpoint inhibitors (ICIs) have achieved great success in the treatment of non-small cell lung cancer (NSCLC) patients. However, the response rate is low. The molecular mechanism involved in the effectiveness of ICIs remains to be elucidated. METHODS: ATRX mutation incidence among human cancers was analyzed from TCGA database. Atrx-deficient Lewis lung cancer cell line (LLC-sgAtrx) was established via AAV-CRISPR. Subcutaneous and metastasis models were established by subcutaneous and intravenous injection of LLC-sgAtrx and LLC-sgNTC cells into female C57BL/6 mice. The mice were treated with anti-PD1, anti-CLTA4 or Rat IgG2a. Tumor volume was determined by Vernier calipers and the IVIS imaging system. The proportions of CD3+ T cells, CD45+ immune cells, and the expression of pMHC I and PDL1 were determined by flow cytometry. The T cell cytotoxicity was determined by co-culture experiment. RESULTS: TCGA data showed that Atrx is a tumor suppressor mutated at high frequency among various human cancers. The tumor volume of mice bearing LLC-sgAtrx was significantly shrinked and the median survival of mice was significantly longer after anti-PD1 and anti-CTLA4 treatment. Flowcytometry results showed that Atrx deficiency increase the penetration of CD3+ T cell into the tumor microenvironment and enhanced antigen presentation after IFNγ stimulation. Additionally, the tumor cells with Atrx deficiency were more easily to be damaged by T cells under IFNγ stimulation. CONCLUSION: The present study demonstrated that Atrx deficiency sensitize lung cancer cells to ICIs by multiple mechanisms. And ATRX may serve as a promising biomarker for ICIs which helps patient stratification and decision making.