Lung cancer cells and their sensitivity/resistance to cisplatin chemotherapy: Role of microRNAs and upstream mediators

Ashrafizadeh, Milad; Zarrabi, Ali; Hushmandi, Kiavash; Hashemi, Farid; Moghadam, Ebrahim Rahmani; Owrang, Marzieh; Hashemi, Fardin; Makvandi, Pooyan; Goharrizi, Mohammad Ali Sheikh Beig; Najafi, Masoud; Khan, Haroon

doi:10.1016/j.cellsig.2020.109871

Cited by 103 publications

(49 citation statements)

References 322 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, studies found that SOX2 regulates the stem cell properties and drug resistance of cancer cells [10], which was consistent with our previous ndings for the role of SOX2 in NSCLC A549/CDDP cells [28].The mechanisms of resistance to cisplatin among different cell types are different and complicated [19]. Notably, SOX2 is involved in cisplatin resistance events [19,29,30]. Emerging downstream targets regulating SOX2, such as cyclin D1, Nanog, SKIL, and PI3K, have been found [5,31,32].…”

Section: Discussionsupporting

confidence: 89%

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Chen

Zhou

et al. 2021

Preprint

View full text Add to dashboard Cite

Objective SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). Methods The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR (qPCR), immunohistochemistry (IHC), and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan-Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. Results A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with high expression of SOX2 survived longer than those with low expression of SOX2. Conclusion siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.

show abstract

Section: Discussionsupporting

confidence: 89%

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Chen

Zhou

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…One of the important aspects is the regulation of CP sensitivity by miRNAs [142]. Furthermore, miRNAs can modulate ROS levels in cells [143,144].…”

Section: Cisplatin Resistancementioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

Self Cite

View full text Add to dashboard Cite

The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

show abstract

“…MiRNAs are considered as master regulators of molecular pathways in cancers (Refs 44–49). MiRNA dysregulation is an obvious finding in cancer, and these short ncRNAs are reliable biomarkers for cancer detection and prognosis (Refs 50, 51).…”

Section: Micrornas In Oncology: An Overviewmentioning

confidence: 99%

MicroRNAs regulating SOX2 in cancer progression and therapy response

Mirzaei

Saebfar²,

Gholami

et al. 2021

Expert Rev. Mol. Med.

Self Cite

View full text Add to dashboard Cite

The proliferation, metastasis and therapy response of tumour cells are tightly regulated by interaction among various signalling networks. The microRNAs (miRNAs) can bind to 3′-UTR of mRNA and down-regulate expression of target gene. The miRNAs target various molecular pathways in regulating biological events such as apoptosis, differentiation, angiogenesis and migration. The aberrant expression of miRNAs occurs in cancers and they have both tumour-suppressor and tumour-promoting functions. On the contrary, SOX proteins are capable of binding to DNA and regulating gene expression. SOX2 is a well-known member of SOX family that its overexpression in different cancers to ensure progression and stemness. The present review focuses on modulatory impact of miRNAs on SOX2 in affecting growth, migration and therapy response of cancers. The lncRNAs and circRNAs can function as upstream mediators of miRNA/SOX2 axis in cancers. In addition, NF-κB, TNF-α and SOX17 are among other molecular pathways regulating miRNA/SOX2 axis in cancer. Noteworthy, anti-cancer compounds including bufalin and ovatodiolide are suggested to regulate miRNA/SOX2 axis in cancers. The translation of current findings to clinical course can pave the way to effective treatment of cancer patients and improve their prognosis.

show abstract

Lung cancer cells and their sensitivity/resistance to cisplatin chemotherapy: Role of microRNAs and upstream mediators

Cited by 103 publications

References 322 publications

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

MicroRNAs regulating SOX2 in cancer progression and therapy response

Contact Info

Product

Resources

About