TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches

Cancer Biology & Therapy

Chen

et al. 2022

Self Cite

Endometrial cancer (EC) is a gynecological malignant tumor characterized by high incidence. EC occurrence and development are regulated by numerous molecules and signal pathways. There is a need to explore key regulatory molecules to identify potential therapeutic targets to reduce the incidence of EC. Treatment by targeting a single molecule is characterized by poor efficacy owing to the development of resistance and significant side effects. The current study explored potential candidates in EC by integrating bioinformatics analysis and in vivo and in vitro experimental validation to circumvent the limitation of low efficacy of currently used molecules. Molecular dynamics simulations provide details at the molecular level of intermolecular regulation. In the current study, MLLT11 and TRIL were identified as important regulatory molecules in EC. The two molecules formed a heteromultimer by binding to AKT protein, which induced its phosphorylation of threonine at position 308. Ultimately, the complex stimulates PI3K/AKT/mTOR signaling pathway, a pivotal pathway in tumors. The findings of the current study show a novel complex, MLLT11-TRIL, which can act as AKT protein agonist, thus inducing activity of PI3K/AKT/mTOR signaling pathway. Targeting MLLT11 and TRIL simultaneously, or blocking the formation of the MLLT11-TRIL complex, can abrogate progression of EC.

Section: Introductionsupporting

confidence: 86%

MLLT11-TRIL complex promotes the progression of endometrial cancer through PI3K/AKT/mTOR signaling pathway

Cancer Biology & Therapy

Chen

et al. 2022

Self Cite

“…The WGCNA package in R software was used to study the correlation patterns between genes as previously described, 14 and the gene modules related to clinical information were obtained. Pearson correlation coefficient between genes were calculated, and a weighted adjacency matrix a mn = |C mn | β was constructed, where a mn represents the adjacency coefficient between gene m and gene n; C mn represents the Pearson correlation coefficient between gene m and gene n. The scale‐free network was ensured by selecting the soft threshold β = 7, and the minimum module size was set to 30 genes.…”

Section: Methodsmentioning

confidence: 99%

“…The WGCNA package in R software was used to study the correlation patterns between genes as previously described, 14 and the gene modules related to clinical information were obtained.…”

Section: Establishment Of Weighted Co-expression Network Analysismentioning

confidence: 99%

Integrated study of miR‐215 promoting breast cancer cell apoptosis by targeting RAD54B

Wang

J Cellular Molecular Medi

Tan

et al. 2021

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Background MicroRNAs (miRNAs) are widely distributed in cells and participate in the regulation of the pathophysiological process of many diseases. As an important part of non‐coding RNA, miRNAs regulate a variety of molecules and signal pathways in tumour cells. However, the evidence for regulatory mechanisms of specific miRNAs in tumour cells is still lacking. Methods In this study, we used transcriptomics analysis and integrated a variety of public databases to screen miRNAs that have key regulatory effects on breast cancer (BC). In addition, we used in vitro and in vivo studies and combined clinical samples to verify its regulatory mechanism. Results We found that among the specific miRNAs, miR‐215‐5p is a key regulator in BC. Compared with normal adjacent tissues, miR‐215‐5p has a lower expression level in BC tissues. Patients with high expression levels of miR‐215‐5p have a longer survival time. miR‐215‐5p can specifically target the 3′UTR region of RAD54B mRNA and down‐regulate the expression of RAD54B, thereby inhibiting the proliferation of BC cells and promoting the apoptosis of BC cells. Conclusions Finally, we found that miR‐215‐5p can be used as an important biomarker for BC. We have clarified its function and revealed its mechanism of targeting RAD54B mRNA for the first time. This may provide important clues to reveal the deeper molecular regulation mechanism of BC.

“…In addition, the pathological process of various diseases, such as cancer, nervous system, and skeletal muscle system diseases are also related to BTB protein (Chaharbakhshi & Jemc, 2016; Jin et al, 2017; Leeman‐Neill & Bhagat, 2018; Y. Liu et al, 2018). In a previous study, we have found that ZBTB41, which is homologous to ZBTB34, was a crucial biomarker affecting the progression of cervical cancer (M. Wang, Liao, et al, 2020). In this study, through comprehensive multidatabase mining, we found that ZBTB34 is a hub gene for CRC progression.…”

Section: Discussionmentioning

confidence: 98%

Lnc‐CPLC promotes the progression of colorectal cancer via regulating ZBTB34 by competitively binding miR‐4319

Journal Cellular Physiology

Liu

Wang

et al. 2021

Self Cite

Long noncoding RNAs (lncRNAs) have been considered as regulatory molecules that play crucial roles in diverse biological processes, including the regulation of tumor progression. However, in colorectal cancer (CRC), due to the complex regulatory relationships involved in lncRNAs, the details of the specific mechanism still need to be elucidated. To discover the key regulatory role of lncRNA in CRC, we used bioinformatics analysis methods for preliminary screening. Through the combination of in vitro and in vivo verification, we further comprehensively analyzed the specific regulation of the key gene and the related key lncRNA in CRC. We found that ZBTB34 and lnc-CPLC (CRC progression-associated lncRNA) had a strong correlation, which plays a key role in the regulation of CRC. Furthermore, by exerting the "sponge" function, lnc-CPLC could bind to miR4319 and release its binding to the 3'UTR of ZBTB34 mRNA. Our results reveal the mechanism of the lnc-CPLC/miR-4319/ZBTB34 signal axis in CRC and provide evidence for elucidating the complex molecular mechanisms in tumors.