Notes

"Role and Significance of lncRNA-miRNA Interplay in Cancer Drug Resistance and Therapeutic Implications"
1. Challenges in Cancer Drug Resistance:
- Cancer drug resistance remains a significant challenge in modern oncology.
- Innovative therapeutic strategies are necessary to overcome drug resistance.

2. Role of Non-Coding RNAs:
- Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play multifaceted roles in drug resistance.
- They orchestrate gene expression and cellular processes, interacting with specific signaling pathways.

3. Effect on Drug Efficacy:
- Dysregulation of lncRNAs and miRNAs leads to the acquisition of drug resistance, reducing the efficacy of conventional treatments.
- Targeting these non-coding RNAs presents potential therapeutic avenues.

4. Therapeutic Strategies:
- Developing specific inhibitors or mimics for lncRNAs and miRNAs, alone or in combination with conventional chemotherapy, is a promising strategy.
- Epigenetic modulators, immunotherapies, and personalized medicine also present exciting prospects in tackling drug resistance.

5. Continued Research and Challenges:
- Substantial progress has been made, but challenges such as target validation and safety assessment remain.
- The need for continued research to overcome these hurdles is emphasized.

6. Transformative Potential:
- The review underscores the transformative potential of lncRNA-miRNA interplay in revolutionizing cancer therapy.
- This interplay has the potential to unlock new therapeutic approaches for overcoming drug resistance.

7. Roles of lncRNAs in Cancer:
- Long non-coding RNAs (lncRNAs) play crucial roles in tumorigenesis and are potential biomarkers for cancer diagnosis.
- They are involved in multidimensional crosstalk with RNA-binding proteins and have diverse functions in cancer biology.

8. Unique Features of lncRNA Biogenesis and Function:
- The biogenesis and function of lncRNAs have unique features that distinguish them from other RNA molecules.
- Their interactions, stability, and localization are regulated by specific RNA motifs and combinatorial predictions.

9. Epigenetic Regulation and Chromatin Structure:
- lncRNAs are involved in the epigenetic regulation of endothelial-to-mesenchymal transition and control of chromatin structure.
- They establish specific chromatin signatures and modulate alternative splicing in the context of chromatin organization.

10. Functional Insights and Interactions:
- lncRNAs have hidden functions and major partner-proteins that contribute to gene expression and DNA processing.
- They regulate alternative splicing and play a role in the DNA damage response and repair in cancer cells.

11. Regulatory Functions and Cancer Pathogenesis:
- Various lncRNAs are highly associated with human cancers and contribute to cancer pathogenesis and treatment resistance.
- MALAT1, HOTAIR, GAS5, MEG3, and H19 are some of the lncRNAs with significant regulatory roles in cancer.

12. Insights into Gene Regulation and Disease Treatment:
- lncRNAs play crucial roles in gene regulation and have potential implications for disease treatment.
- Their functions pose challenges and important recommendations for understanding and studying long non-coding RNAs.

13. Potential Biomarkers and Therapeutic Targets:
- lncRNAs have potential as biomarkers in cancer diagnosis and are emerging as therapeutic targets for different human diseases.
- Their diverse functions and regulatory crosstalk with molecular pathways present opportunities for targeted therapies.

14. Future Directions and Research Implications:
- Understanding the life and competition of competing endogenous RNAs (ceRNAs) provides insights into lncRNA functions.
- Research on noncoding transcription, genome organization, and nuclear speckles has implications for unraveling lncRNA regulatory mechanisms.

15. The Role of lncRNAs in Tumor Angiogenesis:
- Liu X et al. discuss the modulation of MDSCs in the tumor microenvironment by microRNAs/LncRNAs.
- Yousefi H et al. present the classification and mechanisms of LncRNAs in breast cancer metastasis and drug resistance.

16. LncRNAs in Cancer Resistance and Therapy:
- Wang Q et al. demonstrate how HOTAIR induces EGFR-TKIs resistance in non-small cell lung cancer through epithelial-mesenchymal transition.
- Dastmalchi N et al. highlight the potential of LncRNAs as prognostic and diagnostic biomarkers in colorectal cancer.

17. Diagnostic and Therapeutic Potential of LncRNAs in Cancer:
- Khawar MB et al. discuss the diagnostic, prognostic, and therapeutic potential of LncRNAs in cancer.
- Badowski C et al. emphasize blood-derived LncRNAs as biomarkers for cancer diagnosis.

18. Regulatory and Therapeutic Implications of LncRNAs in Cancer:
- Nandwani A et al. explore the regulatory and therapeutic implications of LncRNAs in cancer.
- López-Urrutia E et al. investigate the crosstalk between LncRNAs, micro-RNAs, and mRNAs as master regulators in cancer.

19. Functional Role of LncRNAs in Cancer Treatment and Resistance:
- Sun Q et al. highlight the functions of microRNA-host-gene locus-encoded LncRNAs in cancer.
- Chen B et al. focus on targeting non-coding RNAs to overcome cancer therapy resistance.

20. LncRNAs as Potential Therapeutic Targets in Cancer:
- Bayraktar E et al. provide an update on targeting miRNAs and other non-coding RNAs as a therapeutic approach.
- Kong X et al. analyze LncRNA, miRNA, and mRNA-associated ceRNA networks to identify potential drug targets for drug-resistant non-small cell lung cancer.

21. Role of LncRNAs in Cancer Drug Resistance:
- Zhang J et al. focus on the mechanisms of drug resistance in acute myeloid leukemia.
- Di Martino MT et al. propose miRNAs and LncRNAs as novel therapeutic targets to improve cancer immunotherapy.

22. The Influence of LncRNAs on Cancer Prognosis:
- Du T et al. discuss the role of LncRNAs in drug resistance of breast cancer.
- Chen Y et al. highlight the function and role of LncRNAs in the prediction, diagnosis, and prognosis of lung cancer.

23. Molecular Mechanisms of lncRNAs in Regulating Cancer Cell Radiosensitivity:
- Describes the molecular mechanisms of lncRNAs in regulating cancer cell radiosensitivity.
- Provides insights into the role of long non-coding RNAs in cancer treatment.

24. Advances in the Role of lncRNAs and RNA-Binding Proteins in Regulating DNA Damage Repair in Cancer Cells:
- Discusses the advances in understanding the role of lncRNAs and RNA-binding proteins in regulating DNA damage repair in cancer cells.
- Highlights the potential implications for cancer therapy.

25. The Role of lncRNAs in the Repair of DNA Double Strand Breaks:
- Explores the role of long non-coding RNAs in the repair of DNA double strand breaks.
- Provides insights into the potential impact on cancer treatment.

26. The DNA Damage Repair-Related lncRNAs Signature Predicts the Prognosis and Immunotherapy Response in Gastric Cancer:
- Examines a DNA damage repair-related lncRNAs signature and its predictive value for the prognosis and immunotherapy response in gastric cancer.
- Highlights the potential clinical significance of lncRNAs in cancer treatment.

27. Long Non-Coding RNAs as Emerging Targets in Lung Cancer:
- Explores the emerging role of long non-coding RNAs as targets in lung cancer.
- Addresses the potential implications for lung cancer therapy.

28. Non-Coding RNAs/DNMT3B Axis in Human Cancers: From Pathogenesis to Clinical Significance:
- Discusses the non-coding RNAs/DNMT3B axis in human cancers, spanning from pathogenesis to clinical significance.
- Highlights the potential clinical implications of this axis in cancer management.

29. The Functional Role of Long Noncoding RNA in Resistance to Anticancer Treatment:
- Investigates the functional role of long noncoding RNA in resistance to anticancer treatment.
- Provides insights into potential mechanisms of resistance and therapeutic implications.

30. Mechanisms of Apoptosis-Related Long Non-Coding RNAs in Ovarian Cancer:
- Explores the mechanisms of apoptosis-related long non-coding RNAs in ovarian cancer.
- Addresses the potential implications for ovarian cancer treatment.

31. LncRNA and Cancer Multi-Drug Resistance:
- Studies show that lncRNAs act as multifunctional regulators in cancer multi-drug resistance.
- Understanding the role of lncRNAs in drug resistance could lead to the development of more effective treatments.

32. Dual Roles of MiRNAs and LncRNAs in TGF-β Signaling and Metastasis:
- MiRNAs and LncRNAs play dual roles in TGF-β signaling-regulated metastasis in lung cancer.
- The interaction between miRNAs and LncRNAs could provide new targets for therapeutic interventions.

33. MicroRNA Networks in Drug Resistance of Colon Carcinoma:
- The molecular networks of microRNAs and their targets play a significant role in drug resistance of colon carcinoma.
- Targeting microRNA networks could potentially overcome drug resistance in colon carcinoma.

34. Integration of Non-Coding RNAs in JAK-STAT Regulatory Networks:
- Non-coding RNAs are integrated into JAK-STAT regulatory networks, opening new avenues for targeted therapies.
- Understanding the crosstalk between non-coding RNAs and JAK-STAT signaling may offer novel treatment strategies.

35. Non-Coding RNA and MAPK Signaling Pathway in Liver Cancer:
- Non-coding RNAs are related to the MAPK signaling pathway in liver cancer, highlighting the potential for targeted therapies.
- Exploring non-coding RNA involvement in the MAPK pathway could lead to new therapeutic approaches for liver cancer.

36. NcRNAs and Drug Resistance in Breast Cancer:
- The landscape of NcRNAs is involved in the drug resistance of breast cancer, suggesting novel strategies for improving treatment outcomes.
- Targeting specific NcRNAs associated with drug resistance may enhance the efficacy of breast cancer therapies.

37. Roles of Non-Coding RNAs in Head and Neck Cancers:
- Non-coding RNAs play essential roles in the drug resistance of head and neck cancers, presenting opportunities for targeted interventions.
- Understanding the mechanisms of non-coding RNA involvement in drug resistance could lead to tailored therapies for head and neck cancers.

38. Regulation of Breast Cancer Drug Sensitivity by lncRNA CBR3-AS1:
- LncRNA CBR3-AS1 regulates breast cancer drug sensitivity through the JNK1/MEK4-mediated MAPK signal pathway, offering insights into potential therapeutic targets.
- Targeting the pathway regulated by lncRNA CBR3-AS1 may enhance drug sensitivity in breast cancer.

39. Role of Non-Coding RNAs in Cancer Therapy Resistance:
- Non-coding RNAs and RNA modifiers play a significant role in cancer therapy resistance, impacting potential diagnostic approaches.
- Understanding the mechanisms by which non-coding RNAs contribute to therapy resistance may provide insights for targeted drug development.

40. Epigenetic Modifications for Cancer Therapy:
- Epigenetic modifications have been identified as potential targets for cancer therapy.
- Modulating epigenetic modifications shows promise for enhancing the effectiveness of cancer therapy.

41. Insights into the Regulation of Cancer Stem Cells:
- MicroRNAs and long non-coding RNAs play a role in regulating the function of cancer stem cells and the progression of cancer.
- Understanding the impact of miRNAs and lncRNAs on cancer stem cells presents therapeutic opportunities in cancer treatment.

42. Molecular and Cellular Paradigms of Multidrug Resistance in Cancer:
- Understanding the molecular and cellular paradigms of multidrug resistance in cancer is essential for developing effective treatment strategies.
- Targeting the PI3K/AKT pathway may offer a key link to modulate multidrug resistance in cancers.

43. Long Non-Coding RNAs in Chemoresistance:
- Long non-coding RNAs have been implicated in conferring chemoresistance in cancer cells, highlighting their potential as therapeutic targets.
- Exploring the mechanisms by which lncRNAs contribute to chemoresistance provides opportunities for overcoming drug resistance.

44. Autophagy-Regulating Factors in Tumorigenesis and Drug Resistance:
- Understanding the role and mechanisms of autophagy-regulating factors in tumorigenesis and drug resistance is crucial for developing targeted therapies.
- Targeting autophagy-regulating factors presents a potential strategy for addressing drug resistance in cancer.

45. Insights into miRNA-21 and PDCD4 Targeting Strategies for Glioblastoma:
- Targeting miRNA-21 and PDCD4 holds promise for addressing drug resistance in glioblastoma.
- Exploring the role and mechanisms of action of microRNAs presents opportunities for overcoming drug resistance in cancer.

46. Relationship Between Platinum Drug Resistance and Epithelial–Mesenchymal Transition:
- Understanding the relationship between platinum drug resistance and epithelial–mesenchymal transition is crucial for improving treatment outcomes.
- Insights into the mechanisms underlying drug resistance and epithelial–mesenchymal transition provide avenues for developing effective therapeutic interventions.

47. Contributions:
- Conceptualization and original draft preparation: MTSAO, EA, AHK, MNS, MGA
- Review & editing and visualization: YFM, AA(Ahmed Alawadi), AA(Ali Haslany)

48. Corresponding authors:
- Raed Obaid Saleh
- Sharif Alhajlah

49. Key Focus:
- lncRNA-microRNA axis in cancer drug resistance
- Particular focus on signaling pathways