Starvation induced autophagy promotes the progression of bladder cancer by LDHA mediated metabolic reprogramming

Li, Tinghao; Tong, Hang; Yin, Hubin; Luo, Yi; Zhu, Junlong; Qin, Zijia; Su, Yin; He, Weiyang

doi:10.1186/s12935-021-02303-1

Cited by 20 publications

(17 citation statements)

References 42 publications

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“…Lactate dehydrogenase (LDHA) is a key enzyme in the glycolytic process, and the acidic environment established by glycolysis contributes to the immune escape of cancer cells. Inhibition of LDHA reduces the proliferation of many cancer cells, such as those in kidney [25], breast [26], and bladder cancers [27]. In cervical cancer, downregulation of phosphorylated stress-induced phosphoprotein 1 inhibits the progression of cervical cancer by reducing glycolysis and decreasing the level of LDHA [28].…”

Section: Discussionmentioning

confidence: 99%

The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer

Zhang

Wang

et al. 2023

BMC Cancer

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Background Our previous studies have confirmed that miR-154-5p can regulate pRb expression, and thus, play a tumor suppressor role in HPV16 E7-induced cervical cancer. However, its upstream molecules have not been elucidated in the progression of cervical cancer. This study aimed to explore the role of the miR-154-5p upstream molecule, hsa_circ_0000276 in cervical cancer development and its possible mechanisms of action. Methods We detected differences in whole transcriptome expression profiles of cervical squamous carcinoma and tissues adjacent to cervical cancer tissues from patients using microarray technology to predict circular RNAs (circRNAs) with binding sites to miR-154-5p. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0000276 (which had the strongest binding capacity to miR-154 and was selected as the target molecule) in cervical cancer tissues, followed by in vitro functional assays. Downstream microRNAs (miRNAs) and mRNAs of hsa_circ_0000276 were identified using transcriptome microarray data and databases, while the protein–protein interaction networks were obtained using STRING. A competing endogenous RNA (ceRNA) network centered on hsa_circ_0000276 was constructed using Cytoscape and GO and KEGG databases. Abnormal expression and prognosis of critical downstream molecules were analyzed using gene databases and molecular experiments. qRT-PCR and western blot analysis was performed to verify the expression of candidate genes. Results We identified 4,001 differentially expressed circRNAs between HPV16-positive cervical squamous carcinoma and benign cervical tissues and 760 circRNAs targeting miR-154-5p, including hsa_circ_0000276. hsa_circ_0000276 and miR-154-5p directly bound, and hsa_circ_0000276 was upregulated, in cervical precancerous lesions and cervical cancer tissues and cells. Silencing hsa_circ_0000276 inhibited G1/S transition and cell proliferation and promoted apoptosis in SiHa and CaSki cells. Bioinformatics analysis showed that the hsa_circ_0000276 ceRNA network included 17 miRNAs and seven mRNAs, and downstream molecules of hsa_circ_0000276 were upregulated in cervical cancer tissues. These downstream molecules were associated with a poor prognosis and affected cervical cancer-associated immune infiltration. Of these, expression of CD47, LDHA, PDIA3, and SLC16A1 was downregulated in sh_hsa_circ_0000276 cells. Conclusions Our findings show that hsa_circ_0000276 exerts cancer-promoting effects in cervical cancer and is an underlying biomarker for cervical squamous cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer

Zhang

Wang

et al. 2023

BMC Cancer

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“…A PAGE Gel Fast Preparation Kit (Shanghai Epizyme Biomedical Technology Co., Ltd., Shanghai, China) was selected to prepare 12.5% sodium dodecyl sulfate-polyacrylamide gels to separate the total proteins [ 33 ]. Then, the proteins were transferred to nitrocellulose membranes (Millipore, Burlington, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Cell proliferation was verified by Cell Counting Kit-8 (CCK-8, bimake), EdU (BeyoClick™, Nantong, China, EdU Cell Proliferation Kit with Alexa Fluor 488) and colony formation [ 33 ]. Cells treated under different experimental conditions were inoculated onto 96-well plates at an initial density of 5000 cells per well.…”

Section: Methodsmentioning

confidence: 99%

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YTHDF1 Promotes Bladder Cancer Cell Proliferation via the METTL3/YTHDF1–RPN2–PI3K/AKT/mTOR Axis

Zhu

Tong

Sun

et al. 2023

IJMS

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N6-methyladenosine (m6A) is the most common mRNA modification and it plays a critical role in tumor progression, prognoses and therapeutic response. In recent years, more and more studies have shown that m6A modifications play an important role in bladder carcinogenesis and development. However, the regulatory mechanisms of m6A modifications are complex. Whether the m6A reading protein YTHDF1 is involved in the development of bladder cancer remains to be elucidated. The aims of this study were to determine the association between METTL3/YTHDF1 and bladder cancer cell proliferation and cisplatin resistance to explore the downstream target genes of METTL3/YTHDF1 and to explore the therapeutic implications for bladder cancer patients. The results showed that the reduced expression of METTL3/YTHDF1 could lead to decreased bladder cancer cell proliferation and cisplatin sensitivity. Meanwhile, overexpression of the downstream target gene, RPN2, could rescue the effect of reduced METTL3/YTHDF1 expression on bladder cancer cells. In conclusion, this study proposes a novel METTL3/YTHDF1–RPN2–PI3K/AKT/mTOR regulatory axis that affects bladder cancer cell proliferation and cisplatin sensitivity.

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“…The rapid growth of tumor cells results in malformation of vascular distribution within bladder tumor, further evoking nutrient-deprived conditions [ 14 ]. Starving environment remarkably altered cellular profiles at the levels of gene and protein, and regulated activities of different subpopulations.…”

Section: Introductionmentioning

confidence: 99%

Starvation-induced long non-coding RNAs are significant for prognosis evaluation of bladder cancer

Zhang

Bai

Peng

et al. 2022

Aging

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Background: Starving intratumoral microenvironment prominently alters genic profiles including long noncoding RNAs (lncRNAs), which further regulate bladder cancer (BCa) malignant biological properties, such as invasion and migration. Methods: Transcriptome RNA-sequencing data of 414 BCa tumor tissues and 19 normal tissues were obtained from TCGA database and paired samples of 132 BCa patients. A chain of in vitro validations such as qPCR, migration and invasion assays were performed to reveal the clinical relevance of AC011472.4 and AL157895.1. Results: A total of 11 lncRNAs were identified as starvation-related lncRNAs, of which AC011472.4 and AL157895.1 were relevant to overall survival of BCa patients. Besides, a starvation-related risk score model was established based on the levels of AC011472.4 and AL157895.1. BCa patients with higher levels of AL157895.1 were divided into the high-risk group and usually obtained higher mortality rate, but AC011472.4 was contrary. AL157895.1 expressed highly in BCa cell lines and tumour tissues, especially in patients with the advanced grade, stage and T-stage, while AC011472.4 showed the reversed result. Moreover, increased level of AL157895.1 was remarkably correlated to T-stage, muscle invasion status and distant metastasis. SiRNAsmediated silence of AC011472.4 and AL157895.1 respectively increased and diminished invasion and migration properties of BCa cells. Conclusions: In this study, we highlight the significant roles of AC011472.4 and AL157895.1 on evaluating prognoses of BCa patients and validate their correlation with various clinical parameters. These findings provide an appropriate risk score model for BCa clinical decision making.

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Starvation induced autophagy promotes the progression of bladder cancer by LDHA mediated metabolic reprogramming

Cited by 20 publications

References 42 publications

The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer

The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer

YTHDF1 Promotes Bladder Cancer Cell Proliferation via the METTL3/YTHDF1–RPN2–PI3K/AKT/mTOR Axis

Starvation-induced long non-coding RNAs are significant for prognosis evaluation of bladder cancer

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