Colorectal neoplasia differentially expressed (CRNDE) is a novel gene recognized as a long noncoding RNA (lncRNA) that is highly elevated in colorectal cancer and many other solid tumors but its functions on metastasis and oxaliplatin (OXA) resistance are unknown. In our study, we confirmed the upregulation of CRNDE in both primary specimens from colorectal cancer patients and colorectal cancer cell lines. Knockdown of CRNDE expression inhibited the migration and invasion potency of colorectal cancer cells with no effect on cell apoptosis. Overexpression of CRNDE promoted the migration and invasion potency of colorectal cancer cells. Furthermore, we found that CRNDE conferred chemoresistance in colorectal cancer cells. Knockdown of CRNDE with OXA treatment decreased cell viability and promoted DNA damage and cell apoptosis, while the overexpression of CRNDE with OXA treatment reduced DNA damage and cell apoptosis. Further in-depth mechanistic studies revealed that CRNDE functioned as a competing endogenous RNA for miR-136, led to the de-repression of its endogenous target, E2F transcription factor 1 (E2F1). Overall, our findings demonstrate that CRNDE functions as a competing endogenous RNA to promote metastasis and OXA resistance by sponging miR-136 in colorectal cancer.

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Long noncoding RNA CRNDE functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer.

Increasing evidence has experimentally proved the competitive endogenous RNA (ceRNA) hypothesis that long non-coding RNA (lncRNA) can affect the expression of RNA targets by competitively combining microRNA (miRNA) via miRNA response elements. However, an extensive ceRNA network of thyroid carcinoma in a large cohort has not been evaluated. We analyzed the RNAseq and miRNAseq data of 348 cases of primary papillary thyroid cancer (PTC) patients with clinical information downloaded from The Cancer Genome Atlas (TCGA) project to search for potential biomarkers or therapeutic targets. A computational approach was applied to build an lncRNA-miRNA-mRNA regulatory network of PTC. In total, 780 lncRNAs were detected as collectively dysregulated lncRNAs in all 3 PTC variants compared with normal tissues (fold change >2 and false discovery rate <0.05). The interactions among 45 lncRNAs, 13 miRNAs and 86 mRNAs constituted a ceRNA network of PTC. Nine out of the 45 aberrantly expressed lncRNAs were related to the clinical features of PTC patients. However, the expression levels of 3 lncRNAs (LINC00284, RBMS3-AS1 and ZFX-AS1) were identified to be tightly correlated with the patients overall survival (log-rank, P<0.05). The present study identified a list of specific lncRNAs associated with PTC progression and prognosis. This complex ceRNA interaction network in PTC may provide guidance for better understanding the molecular mechanisms underlying PTC.

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Construction and investigation of lncRNA-associated ceRNA regulatory network in papillary thyroid cancer

Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunotherapy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer.

https://www.mdpi.com/1422-0067/22/12/6532/pdf

Ovarian Cancer Immunotherapy and Personalized Medicine

Cancer and stromal cells, which include (cancer-associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation. Further, the stroma vasculature impacts the metabolism of the cells by providing or limiting the availability of oxygen and nutrients. Autophagy, a lysosomal catabolic process with homeostatic and prosurvival functions, influences the behavior of cancer cells, affecting a variety of processes such as the survival in metabolic harsh conditions, the invasive growth, the development of immune and chemo resistance, the maintenance of stem-like properties, and dormancy. Further, autophagy is involved in the secretion and the signaling of promigratory cytokines. Cancer-associated fibroblasts can influence the actual level of autophagy in ovarian cancer cells through the secretion of pro-inflammatory cytokines and the release of autophagy-derived metabolites and substrates. Interrupting the metabolic cross-talk between cancer cells and cancer-associated fibroblasts could be an effective therapeutic strategy to arrest the progression and prevent the relapse of ovarian cancer.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/med.21473

The metabolic cross-talk between epithelial cancer cells and stromal fibroblasts in ovarian cancer progression: Autophagy plays a role

Cisplatin, as the first-line anti-tumor agent, is widely used for treatment of a variety of malignancies including non-small cell lung cancer (NSCLC). However, the acquired resistance has been a major obstacle for the clinical application. Scutellarin is a active flavone extracted from Erigeron breviscapus Hand-Mazz that has been shown to exhibit anticancer activities on various types of tumors. Here, we reported that scutellarin was capable of sensitizing A549/DDP cells to cisplatin by enhancing apoptosis and autophagy. Mechanistic analyses indicated that cisplatin-induced caspase-3-dependent apoptosis was elevated in the presence of scutellarin through activating extracellular signal-regulated kinases (ERK)-mediated p53 pathway. Furthermore, scutellarin also promoted cisplatin-induced cytotoxic autophagy, downregulated expression of p-AKT and c-met. Deficiency of c-met reduced p-AKT level, and inhibition of p-AKT or c-met improved autophagy in A549/DDP cells. Interestingly, loss of autophagy attenuated the synergism of this combination. In vivo, the co-treatment of cisplatin and scutellarin notably reduced the tumor size when compared with cisplatin treatment alone. Notably, scutellarin significantly reduced the toxicity generated by cisplatin in tumor-bearing mice. This study identifies the unique role of scutellarin in reversing cisplatin resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.

/pdf/scutellarin-increases-cisplatin-induced-apoptosis-and-2ueah4npxk.pdf

Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways.

Autophagy is a conserved cellular self-digestion pathway for maintenance of homeostasis under basal and stressed conditions. Autophagy plays pivotal roles in the pathogenesis of many diseases, such as aging-related diseases, autoimmune diseases, cardiovascular diseases, and cancers. Of special note is that accumulating data suggest an intimate relationship between autophagy and ovarian carcinoma. Autophagy is well identified to act as either as a tumor-suppressor or as a tumor-promoter in ovarian carcinoma. The exact function of autophagy in ovarian carcinoma is highly dependent on the circumstances of cancer including hypoxic, nutrient-deficient, chemotherapy and so on. However, the mechanism underlying autophagy associated with ovarian carcinoma remains elusive, the precise role of autophagy in ovarian carcinoma also remains undetermined. In this review, we tried to sum up and discuss recent research achievements of autophagy in ovarian cancer. Moreover, waves of novel therapies ways for ovarian carcinoma based on the functions of autophagy were collected.

https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=13080&path%5B%5D=41445

Autophagy as an emerging therapy target for ovarian carcinoma.

E2F is a family of transcription factors that recognized to regulate the expression of genes essential for a wide range of cellular functions, including cell cycle progression, DNA repair, DNA replication, differentiation, proliferation, and apoptosis. E2F1, the most classic member of the E2F family, exhibits a complex role in tumor development regulation. In recent years, a growing body of data suggested an intimate relationship between E2F1 and ovarian carcinoma. And E2F1 was well identified to play dual functions and serve as a useful prognostic indicator in ovarian carcinoma. However, the mechanism underlying E2F1 associated with ovarian carcinoma remains elusive. It is necessary to clarify the fundamental role of E2F1 in ovarian carcinoma. In this review, we tried to sum up the knowledge of E2F1, including its structure and related mechanism. We also attempt to absorb the research achievements and collect the mechanism of E2F1 in ovarian carcinoma.

E2F1: a promising regulator in ovarian carcinoma.

Immunotherapy is a novel clinical approach that has shown clinical efficacy in multiple cancers. However, only a fraction of patients respond well to immunotherapy. Immuno-oncological studies have identified the type of tumors that are sensitive to immunotherapy, the so-called hot tumors, while unresponsive tumors, known as "cold tumors," have the potential to turn into hot ones. Therefore, the mechanisms underlying cold tumor formation must be elucidated, and efforts should be made to turn cold tumors into hot tumors. N6-methyladenosine (m6A) RNA modification affects the maturation and function of immune cells by controlling mRNA immunogenicity and innate immune components in the tumor microenvironment (TME), suggesting its predominant role in the development of tumors and its potential use as a target to improve cancer immunotherapy. In this review, we first describe the TME, cold and hot tumors, and m6A RNA modification. Then, we focus on the role of m6A RNA modification in cold tumor formation and regulation. Finally, we discuss the potential clinical implications and immunotherapeutic approaches of m6A RNA modification in cancer patients. In conclusion, m6A RNA modification is involved in cold tumor formation by regulating immunity, tumor-cell-intrinsic pathways, soluble inhibitory mediators in the TME, increasing metabolic competition, and affecting the tumor mutational burden. Furthermore, m6A RNA modification regulators may potentially be used as diagnostic and prognostic biomarkers for different types of cancer. In addition, targeting m6A RNA modification may sensitize cancers to immunotherapy, making it a promising immunotherapeutic approach for turning cold tumors into hot ones.

/pdf/n6-methyladenosine-rna-modification-an-emerging-6wdijl21me.pdf

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors.

Background: Cesarean scar pregnancy (CSP), a rare type of ectopic pregnancy, can lead to adverse pregnancy outcomes. However, there is no uniform international treatment guideline for CSP. In this study, we retrospectively analyzed the advantages and disadvantages of three different surgical methods for type II CSP, trying to find the best treatment plan. Methods: From January 2013 to December 2018, a retrospective analysis was performed in 58 patients with type II CSP admitted to the Department of Gynecology, Second Affiliated Hospital of Anhui Medical University. 20 patients underwent hysteroscopic resection (Group A), 18 patients underwent laparoscopic resection and repair (Group B), and 20 patients underwent vaginal resection and repair (Group C). All patients were treated with preventive uterine artery embolization (UAE) preoperatively. The clinical data were collected, and the treatment effects of the different surgical methods were compared. Results: Age, gravidity, parity, number of previous cesarean sections, time period since the last cesarean section, menolipsis days, and preoperative level of the beta-subunit of human chorionic gonadotropin (β-hCG) were not significant different among the three groups (P> 0.05). The differences in operation time (46.85±20.91 min vs. 105.78±32.95 min vs. 67.85±32.88 min), intraoperative blood loss (45.00 ± 17.32 mL vs. 262.22 ± 235.74 mL vs. 166.50 ± 150.66 mL), postoperative hemoglobin level decreased (11.60 ± 5.60 g/L vs. 20.11 ± 7.72 g/L vs. 14.95 ± 5.40 g/L), and menstrual cycle recovery time (35.40 ± 6.31 day vs. 30.11 ± 5.04 day vs. 30.80 ± 4.62 day) were significant different. Conclusions: Hysteroscopic, laparoscopic, and transvaginal surgery can effectively treat type II CSP. Treatment should be individualized according to the diameter of the gestational sac, the patient's fertility requirements as well as the doctor's surgical experience and the surgical equipment of the local hospital.

Lei Zhan

Papers

Autophagy as an emerging therapy target for ovarian carcinoma.

E2F1: a promising regulator in ovarian carcinoma.

N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors.

Surgical management for type II cesarean scar pregnancy