Exosomal lncRNA SCIRT/miR-665 Transferring Promotes Lung Cancer Cell Metastasis through the Inhibition of HEYL

Xia

Clinical Laboratory Analysis

2022

Background Circular RNAs (circRNAs) are attractive candidates to be used as biomarkers of human cancers, including lung adenocarcinoma (LUAD). Our study aimed to investigate the functions and regulatory mechanisms of hsa_circ_0129047 in the tumorigenesis of LUAD. Methods Reverse transcription‐quantitative polymerase chain reaction was performed to determine the circRNA, microRNA (miRNA), and mRNA expression levels in LUAD cell lines and tissues. Tumor xenografts were established in nude mice to evaluate whether hsa_circ_0129047 affected LUAD tumor development in vivo. Cell counting kit‐8 and transwell assays were performed to assess the mechanisms by which hsa_circ_0129047 influenced the viability and migration of LUAD cells, respectively. Apoptosis was evaluated via determination of the levels of the apoptotic markers, B‐cell lymphoma‐2, and Bcl‐2‐associated X, via Western blotting. Dual‐luciferase reporter assay, RNA immunoprecipitation assay, and Pearson's correlation analysis were performed to determine the relationships among miR‐375 and hsa_circ_0129047 and activin A receptor‐like type 1 (ACVRL1). Results Downregulation of hsa_circ_0129047 levels was observed in LUAD cell lines and tissues. Meanwhile, the upregulation of hsa_circ_0129047 levels repressed the proliferative, migratory, and survival capacities of LUAD cells in vitro. Hsa_circ_0129047 exerted antitumor effects during in vivo tumor development. Finally, we demonstrated that hsa_circ_0129047 sponged miR‐375. This interaction facilitated the expression of the downstream target of miR‐375, ACVRL1, whose upregulation inhibited the development and malignancy of LUAD. Conclusion These findings demonstrate that hsa_circ_0129047 functions as a tumor inhibitor in LUAD by modulating the miR‐375/ACVRL1 axis. Hence, hsa_circ_0129047 may be a promising biomarker and gene target for LUAD treatment.

Section: Discussionmentioning

confidence: 94%

Hsa_circ_0129047 regulates the miR‐375/ACVRL1 axis to attenuate the progression of lung adenocarcinoma

Xia

Clinical Laboratory Analysis

2022

“…A large number of factors can be carried by EVs into NSCLC cells which play a role in NSCLC, including lncRNAs [ 16 , 43 , 44 ]. Following literature review and selection of related genes, we speculated that EVs may carry the following factors to exert an impact in NSCLC: lncRNA-LINC00662, lncRNA-TBILA, lncRNA-SNHG12, miR-744, and miR-378 [ 19 , 43 , 45–47 ].…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, EVs are known to possess the ability to carry lncRNAs into NSCLCs to modulate the progression of numerous malignancies [ 43 , 44 ]. One such lncRNA, namely lncRNA SNHG12, was previously found to be up-regulated in human osteosarcoma cells and NSCLC cells, along with the promotion of cell growth and proliferation [ 18 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA SNHG12 in extracellular vesicles derived from carcinoma-associated fibroblasts promotes cisplatin resistance in non-small cell lung cancer cells

Tan¹,

Li²,

Zhang³

et al. 2022

Bioengineered

Non-small-cell lung cancer (NSCLC) is defined as the most universally diagnosed class of lung cancer. Cisplatin (DDP) is an effective drug for NSCLC, but tumors are prone to drug resistance. The current study set out to evaluate the regulatory effect of long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) in extracellular vesicles (EVs) derived from carcinoma-associated fibroblasts (CAFs) on DDP resistance in NSCLC cells. Firstly, NSCLC cells were treated with EVs, followed by detection of cell activity, IC 50 values, cell proliferation and apoptosis, and Cy3-SNHG12. We observed that CAFs-EVs promoted IC 50 values and cell proliferation and inhibited apoptosis. In addition, we learned that lncRNA SNHG12 carried by CAFs-EVs into NSCLC facilitated DDP resistance of NSCLC cells. Furthermore, ELAV like RNA binding protein 1 (HuR/ELAVL1) binding to lncRNA SNHG12 and X-linked inhibitor of apoptosis (XIAP) was verified and RNA stability of XIAP was also verified CAFs-EVs promoted RNA stability and transcription of XIAP, while silencing HuR could partially-reverse this promoting effect. Further joint experimentation showed that silencing XIAP partially inhibited DDP resistance in NSCLC cells. Additionally, the tumor growth and the positive rate of Ki67 and HuR were detected, which showed that CAFs-oe-EVs promoted the tumor and the positive rate of Ki67, as well as the levels of lncRNA SNHG12, HuR, and XIAP in vivo . Collectively, our findings indicated that lncRNA SNHG12 carried by CAFs-EVs into NSCLC cells promoted RNA stability and XIAP transcription by binding to HuR, thus augmenting DDP resistance in NSCLC cells.

“…LncRNAs are mainly transcribed by RNA polymerase II, typically by a 5′7-methylguanosine cap and a 3′ poly (A) tail. Similar to messenger RNAs, they are involved in the pathogenesis of cancer [ 11 , 13 , 14 , 15 , 16 , 17 , 18 ]. Different classes of lncRNAs are generated from introns, exons, intergenic regions, telomerases, enhancers, or promoters [ 19 ].…”

Section: Long Non-coding Rnas and Potential Therapeutic Targeting In ...mentioning

confidence: 99%

The Regulatory Functions and the Mechanisms of Long Non-Coding RNAs in Cervical Cancer

Yang

Al-Hendy

2022

Cells

Cervical cancer is one of the leading causes of death in gynecology cancer worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer. Still, other factors also contribute to cervical cancer development because these cancers commonly arise decades after initial exposure to HPV. So far, the molecular mechanisms underlying the pathogenesis of cervical cancer are still quite limited, and a knowledge gap needs to be filled to help develop novel strategies that will ultimately facilitate the development of therapies and improve cervical cancer patient outcomes. Long non-coding RNAs (lncRNAs) have been increasingly shown to be involved in gene regulation, and the relevant role of lncRNAs in cervical cancer has recently been investigated. In this review, we summarize the recent progress of ascertaining the biological functions of lncRNAs in cervical cancer, from the perspective of cervical cancer proliferation, invasion, and metastasis. In addition, we provide the current state of knowledge by discussing the molecular mechanisms underlying the regulation and emerging role of lncRNAs in the pathogenesis of cervical cancer. Comprehensive and deeper insights into lncRNA-mediated alterations and interactions in cellular events will help develop novel strategies to treat patients with cervical cancer.