Cervical cancer is as a kind of cancer beginning from the cervix. Given that cervical cancer could be observed in women who infected with papillomavirus, regular oral contraceptives, and multiple pregnancies. Early detection of cervical cancer is one of the most important aspects of the therapy of this malignancy. Despite several efforts, finding and developing new biomarkers for cervical cancer diagnosis are required. Among various prognostic, diagnostic, and therapeutic biomarkers, miRNA have been emerged as powerful biomarkers for detection, treatment, and monitoring of response to therapy in cervical cancer. Here, we summarized various miRNAs as an employable platform for prognostic, diagnostic, and therapeutic biomarkers in the treatment of cervical cancer.

microRNAs: New prognostic, diagnostic, and therapeutic biomarkers in cervical cancer.

Background Tumor microenvironment (TME) plays important roles in different cancers. Our study aimed to identify molecules with significant prognostic values and construct a relevant Nomogram, immune model, competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD). Methods "GEO2R," "limma" R packages were used to identify all differentially expressed mRNAs from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Genes with P-value 2 or <-2 were included for further analyses. The function analysis of 250 overlapping mRNAs was shown by DAVID and Metascape software. By UALCAN, Oncomine and R packages, we explored the expression levels, survival analyses of CDK2 in 33 cancers. "Survival," "survminer," "rms" R packages were used to construct a Nomogram model of age, gender, stage, T, M, N. Univariate and multivariate Cox regression were used to establish prognosis-related immune forecast model in LUAD. CeRNA network was constructed by various online databases. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to explore correlations between CDK2 expression and IC50 of anti-tumor drugs. Results A total of 250 differentially expressed genes (DEGs) were identified to participate in many cancer-related pathways, such as activation of immune response, cell adhesion, migration, P13K-AKT signaling pathway. The target molecule CDK2 had prognostic value for the survival of patients in LUAD (P = 5.8e-15). Through Oncomine, TIMER, UALCAN, PrognoScan databases, the expression level of CDK2 in LUAD was higher than normal tissues. Pan-cancer analysis revealed that the expression, stage and survival of CDK2 in 33 cancers, which were statistically significant. Through TISIDB database, we selected 13 immunodepressants, 21 immunostimulants associated with CDK2 and explored 48 genes related to these 34 immunomodulators in cBioProtal database (P < 0.05). Gene Set Enrichment Analysis (GSEA) and Metascape indicated that 49 mRNAs were involved in PUJANA ATM PCC NETWORK (ES = 0.557, P = 0, FDR = 0), SIGNAL TRANSDUCTION (ES = -0.459, P = 0, FDR = 0), immune system process, cell proliferation. Forest map and Nomogram model showed the prognosis of patients with LUAD (Log-Rank = 1.399e-08, Concordance Index = 0.7). Cox regression showed that four mRNAs (SIT1, SNAI3, ASB2, and CDK2) were used to construct the forecast model to predict the prognosis of patients (P < 0.05). LUAD patients were divided into two different risk groups (low and high) had a statistical significance (P = 6.223e-04). By "survival ROC" R package, the total risk score of this prognostic model was AUC = 0.729 (SIT1 = 0.484, SNAI3 = 0.485, ASB2 = 0.267, CDK2 = 0.579). CytoHubba selected ceRNA mechanism medicated by potential biomarkers, 6 lncRNAs-7miRNAs-CDK2. The expression of CDK2 was associated with IC50 of 89 antitumor drugs, and we showed the top 20 drugs with P < 0.05. Conclusion In conclusion, our study identified CDK2 related immune forecast model, Nomogram model, forest map, ceRNA network, IC50 of anti-tumor drugs, to predict the prognosis and guide targeted therapy for LUAD patients.

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Identification of CDK2-Related Immune Forecast Model and ceRNA in Lung Adenocarcinoma, a Pan-Cancer Analysis.

Based on many studies, trichosanthin (TCS) has an antiviral effect that regulates immune response, and targets cancer cells to exert broad-spectrum anti-tumor pharmacological activities. It is speculated that TCS may be a potential natural active drug for preventing as well as treating cervical cancer. But the clearer impact along with underlying TCS mechanism on cervical cancer are still unclear. The purpose of this study is to investigate the function and potential mechanism of TCS in cervical cancer. We measured the viability of cervical cancer cell lines (HeLa & caski cells) using CCK-8 analysis, detected cell proliferation efficiency through Ki-67 staining, analyzed cell apoptosis rate via flow cytometry as well as annexin V-FITC/PI double staining, performed apoptosis-related protein expression through western blotting, evaluated cell migration along with invasion by wound as well as transwell assays, carried out MMP via JC-1 and Rh123 fluorescent probes, as well as detected intracellular ATP and ROS levels by flow cytometry, respectively, to evaluate the effects of TCS. We found that TCS inhibited viability along with proliferation, induced apoptosis, as well as inhibited HeLa & caski cell migration along with invasion in a time- and dose-dependent manner. Additionally, TCS also reduced MMP, and the production of adenosine triphosphate, as well as induced the increase of intracellular reactive oxygen species in cancer cell lines. In accordance with the present studies, TCS inhibits HeLa & caski cell proliferation along with migration but promotes their apoptosis, which may be mediated by regulating oxidative stress.

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2021.1930335

Trichosanthin inhibits cervical cancer by regulating oxidative stress-induced apoptosis.

Cancer is one of the most frequently diagnosed malignant diseases worldwide, posing a serious, long-term threat to patients’ health and life. Systemic chemotherapy remains the first-line therapeutic approach for recurrent or metastatic cancer patients after surgery, with the potential to effectively extend patient survival. However, the development of drug resistance seriously limits the clinical efficiency of chemotherapy and ultimately results in treatment failure and patient death. A large number of studies have shown that non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, are widely involved in the regulation of cancer drug resistance. Their dysregulation contributes to the development of cancer drug resistance by modulating the expression of specific target genes involved in cellular apoptosis, autophagy, drug efflux, epithelial-to-mesenchymal transition (EMT), and cancer stem cells (CSCs). Moreover, some ncRNAs also possess great potential as efficient, specific biomarkers in diagnosis and prognosis as well as therapeutic targets in cancer patients. In this review, we summarize the recent findings on the emerging role and underlying mechanisms of ncRNAs involved in cancer drug resistance and focus on their clinical applications as biomarkers and therapeutic targets in cancer treatment. This information will be of great benefit to early diagnosis and prognostic assessments of cancer as well as the development of ncRNA-based therapeutic strategies for cancer patients.

https://www.frontiersin.org/articles/10.3389/fonc.2022.951864/pdf

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

Cervical cancer (CC) is the fourth most common cancers among women worldwide T-box transcription factor 1 (TBX1), a member of the T-box family, has anti-tumor effects in some types of cancer, but its role in CC is yet unknown The aim of this study is to investigate the functions and underlying mechanisms of TBX1 in CC Online database UALCAN showed that TBX1 was down-regulated in CC tissues compared with normal tissues and patients with lower TBX1 expression level had a poor prognosis TBX1 overexpression significantly decreased the proliferation, migration, and invasion of Hela and SiHa cells Conversely, cell apoptosis and chemosensitivity to cisplatin were promoted in TBX1-overexpressing CC cells Moreover, up-regulation of TBX1 inhibited both AKT and MAPK signaling pathways Furthermore, dual luciferase report assay indicated that TBX1 could directly bind to miR-6727-5p In addition, TBX1 expression was inhibited by miR-6727-5p mimic and up-regulated by miR-6727-5p inhibitor Knockdown of TBX1 reversed the inhibitory effect of the miR-6727-5p inhibitor on CC cells This study demonstrates that TBX1, a target gene of miR-6727-5p, acts as a tumor suppressor in CC, indicating that TBX1 may be a new target for CC therapy

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2021.1880732

T-box transcription factor TBX1, targeted by microRNA-6727-5p, inhibits cell growth and enhances cisplatin chemosensitivity of cervical cancer cells through AKT and MAPK pathways

PURPOSE To study the influence of hsa-miR-6727-5p on the proliferation, apoptosis, invasion and migration of Caski, Hela and SiHa cervical cancer cells. METHODS The CCK8 test, flow cytometry, Transwell and scratch healing experiments were used to measure the influence of hsa-miR-6727-5p on the proliferation, apoptosis, invasion and migration of Caski, Hela and SiHa cells. RESULTS Compared with the negative control (empty vector) group, the hsa-miR-6727-5p expression in the cells transfected with hsa-miR-6727-5p mimics showed a significant increase (p<0.01). CCK8 results showed that the hsa-miR-6727-5p overexpression enhanced significantly the proliferation of cervical cancer cells. Annexin V FITC/PI staining cell results showed that hsa-miR-6727-5p overexpression strongly inhibited the cervical cancer cells apoptosis. Transwell invasion in vitro test showed that hsamiR-6727-5p overexpression significantly enhanced the invasion ability of cervical cancer cells. The scratch healing test suggested that, compared with the control group, the migration ability of cells transfected with hsa-miR-6727-5p mimics in the experimental group was stronger. CONCLUSION We confirmed at the cellular level that hsa-miR-6727-5p promoted the proliferation, invasion and migration of cervical cancer cells and inhibited the apoptosis through the overexpression or inhibition of hsa-miR-6727-5p. These results indicated that hsamiR-6727-5p played a role in promoting the cervical cancer.

Mei Song

Papers

T-box transcription factor TBX1, targeted by microRNA-6727-5p, inhibits cell growth and enhances cisplatin chemosensitivity of cervical cancer cells through AKT and MAPK pathways

Influence of hsa-miR-6727-5p on the proliferation, apoptosis, invasion and migration of Caski, Hela and SiHa cervical cancer cells.