Oct4 transcriptionally regulates the expression of long non-coding RNAs NEAT1 and MALAT1 to promote lung cancer progression

Lung cancer is one of the deadliest forms of cancer affecting society today. Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), through the transcriptional, post-transcriptional, and epigenetic changes they impose, have been found to be dysregulated to affect lung cancer tumorigenesis and metastasis. This review will briefly summarize hallmarks involved in lung cancer initiation and progression. For initiation, these hallmarks include tumor initiating cells, immortalization, activation of oncogenes and inactivation of tumor suppressors. Hallmarks involved in lung cancer progression include metastasis and drug tolerance and resistance. The targeting of these hallmarks with non-coding RNAs can affect vital metabolic and cell signaling pathways, which as a result can potentially have a role in cancerous and pathological processes. By further understanding non-coding RNAs, researchers can work towards diagnoses and treatments to improve early detection and clinical response.

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Crosstalk of long non-coding RNAs and EMT: Searching the missing pieces of an incomplete puzzle for lung cancer therapy

Current Cancer Drug Targets ◽

10.2174/1568009621666210203110305 ◽

2021 ◽

Vol 21 ◽

Author(s):

Milad Ashrafizadeh ◽

Md Shahinozzaman ◽

Sima Orouei ◽

Vahideh Zarrin ◽

Kiavash Hushmandi ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Therapy ◽

Cancer Cells ◽

Cancer Progression ◽

Epithelial To Mesenchymal Transition ◽

Lung Cancer Cells ◽

Mesenchymal Transition ◽

Life Threatening ◽

Non Coding Rnas ◽

Potential Factors

Background: Lung cancer is considered to be the first place among the cancer-related deaths worldwide and demands novel strategies in the treatment of this life-threatening disorder. The aim of this review is to explore regulation of epithelial-to-mesenchymal transition (EMT) by long non-coding RNAs (lncRNAs) in lung cancer. Introduction: LncRNAs can be considered as potential factors for targeting in cancer therapy, since they regulate a bunch of biological processes, e.g. cell proliferation, differentiation and apoptosis. The abnormal expression of lncRNAs occurs in different cancer cells. On the other hand, epithelial-to-mesenchymal transition (EMT) is a critical mechanism participating in migration and metastasis of cancer cells. Method: Different databases including Googlescholar, Pubmed and Sciencedirect were used for collecting articles using keywords such as “LncRNA”, “EMT”, and “Lung cancer”. Result: There are tumor-suppressing lncRNAs that can suppress EMT and metastasis of lung cancer cells. Expression of such lncRNAs undergoes down-regulation in lung cancer progression and restoring their expression is of importance in suppressing lung cancer migration. There are tumor-promoting lncRNAs triggering EMT in lung cancer and enhancing their migration. Conclusion: LncRNAs are potential regulators of EMT in lung cancer, and targeting them, both pharmacologically and genetically, can be of importance in controlling migration of lung cancer cells.

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Silencing linc00662 inhibits cell proliferation and colony formation of lung cancer cells via regulating miR-145-5p/PAFAH1B2 axis

Biochemistry and Cell Biology ◽

10.1139/bcb-2019-0396 ◽

2020 ◽

Author(s):

Zhe-yuan Xu ◽

Jun Peng ◽

Zhi-zhou Shi ◽

Xin-long Chen ◽

Hong-zhong Cheng ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Colony Formation ◽

Lung Squamous Cell Carcinoma ◽

Inhibitory Effects ◽

Competing Endogenous Rna ◽

Protein Levels ◽

The World ◽

H460 Cells ◽

Non Coding Rnas

Lung cancer is the most common cause of cancer-related death in the world. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotides transcripts which are not translated into protein. Linc00662 is overexpressed in lung cancer. However, the roles of linc00662 involved in lung cancer progression are still unknown. In our study, we found that linc00662 was overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by analyzing the TCGA data. We knockdown the linc00662 expression using siRNAs and found that silencing linc00662 significantly inhibited the proliferation and colony formation of A549 and H460 cells. We further found that knockdown of linc00662 increased the miR-145-5p expression and decreased PAFAH1B2 expression. We further showed that linc00662 could bind with miR-145-5p, and miR-145-5p could bind to the 3’UTR of PAFAH1B2. miR-145-5p could negatively regulate PAFAH1B2 both in the mRNA and protein levels. Loss of miR-145-5p could abolish the inhibitory effects of silencing linc00662 on the proliferation and colony formation of A549 and H460 cells. All these findings revealed that linc00662 functioned as an oncogene by acting as competing endogenous RNA (ceRNA) to sponge and regulate miR-145-5p in lung cancer and may provide a potential target of lung cancer treatment.

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Hidden Treasures: Macrophage Long Non-Coding RNAs in Lung Cancer Progression

Cancers ◽

10.3390/cancers13164127 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4127

Author(s):

Annika Karger ◽

Rajender Nandigama ◽

Albrecht Stenzinger ◽

Friedrich Grimminger ◽

Soni Savai Pullamsetti ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Tumor Development ◽

Cell Type ◽

Cellular Mechanisms ◽

Rna Transcripts ◽

Whole Genomes ◽

Major Cell Type ◽

Non Coding Rnas ◽

In The Beginning

Ever since RNA sequencing of whole genomes and transcriptomes became available, numerous RNA transcripts without having the classic function of encoding proteins have been discovered. Long non-coding RNAs (lncRNAs) with a length greater than 200 nucleotides were considered as “junk” in the beginning, but it has increasingly become clear that lncRNAs have crucial roles in regulating a variety of cellular mechanisms and are often deregulated in several diseases, such as cancer. Lung cancer is the leading cause of cancer-related deaths and has a survival rate of less than 10%. Immune cells infiltrating the tumor microenvironment (TME) have been shown to have a great effect on tumor development with macrophages being the major cell type within the TME. Macrophages can inherit an inflammatory M1 or an anti-inflammatory M2 phenotype. Tumor-associated macrophages, which are predominantly polarized to M2, favor tumor growth, angiogenesis, and metastasis. In this review, we aimed to describe the complex roles and functions of lncRNAs in macrophages and their influence on lung cancer development and progression through the TME.

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M6A associated TSUC7 inhibition contributed to Erlotinib Resistance in Lung Adenocarcinoma through a Notch Signaling Activation Dependent Way

10.21203/rs.3.rs-741572/v1 ◽

2021 ◽

Author(s):

Kai Li ◽

Zi-Yang Peng ◽

Shan Gao ◽

Qing-Shi Wang ◽

Rui Wang ◽

...

Keyword(s):

Lung Cancer ◽

Notch Signaling ◽

Cancer Progression ◽

Kinase Inhibitors ◽

Therapy Resistance ◽

Disease Recurrence ◽

Specific Gene ◽

Dependent Manner ◽

Non Coding Rnas ◽

Signaling Activation

Abstract BackgroundThe small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects. MethodsMultiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections. ResultsWe explored the specific gene features of candidates in association with resistance, and found the miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, and then contributed to the resistant features. Functionally, m6A controlled the stemness of EMT features through METTL3 and YTHDF2, and resulted in resistance in PC9ER and HCC827ER cells. The sponging regulation of TUSC7 toward to miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells’ renewal in PC9ER and HCC827ER cells. The Notch signaling functions manipulated the cMYC and DICER inner cytoplasm, and the absence of either cMYC or DICER1 lead to TUSC7 and miR-146a decreasing respectively, formed the closed circle to maintain the balance. ConclusionPC9ER and HCC827ER cells harbored much more stem-like cells, and the resistance could be reversed by Notch signaling inactivation. The intrinsic miR-146 and TUSC7 levels are monitored by m6A effectors, miR-146 and TUSC7 themselves formed the circling loop to sustain the homeostasis. Further in clinics, the combined using of TKIs and Notch specific inhibitory non-coding RNAs will pave the way for yielding the susceptibility to targeted therapy in lung cancer.

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M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02137-9 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Kai Li ◽

Zi-Yang Peng ◽

Shan Gao ◽

Qing-Shi Wang ◽

Rui Wang ◽

...

Keyword(s):

Lung Cancer ◽

Notch Signaling ◽

Cancer Progression ◽

Kinase Inhibitors ◽

Therapy Resistance ◽

Disease Recurrence ◽

Specific Gene ◽

Dependent Manner ◽

Non Coding Rnas ◽

Signaling Activation

Abstract Background The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects. Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections. Results We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells’ renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells. The Notch signaling functions manipulated the cMYC and DICER inner cytoplasm, and the absence of either cMYC or DICER1 lead to TUSC7 and miR-146a decreasing respectively, formed the closed circle to maintain the balance. Conclusion PC9ER and HCC827ER cells harbored much more stem-like cells, and the resistance could be reversed by Notch signaling inactivation. The intrinsic miR-146 and TUSC7 levels are monitored by m6A effectors, the alternation of either miR-146 or TUSC7 expression could lead to the circling loop to sustain the new homeostasis. Further in clinics, the combined delivery of TKIs and Notch specific inhibitory non-coding RNAs will pave the way for yielding the susceptibility to targeted therapy in lung cancer.

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