Knockdown Long Non-coding RNA HCP5 Enhances the Radiosensitivity of Esophageal Carcinoma by Modulating AKT Signaling Activation

Overview

Journal Bioengineered

Date 2021 Dec 31

PMID 34969363

Citations 7

Authors

Yue Guo

Lan Wang

Hui Yang

Nannan Ding

Affiliations

Soon will be listed here.

Abstract

Recently, long noncoding RNAs (lncRNAs) have been revealed to participate in cancer therapy. Especial in tumor radiotherapy, lncRNAs usually could enhance or restrict the radiosensitivity in different ways. LncRNA HCP5 is highly expressed in esophageal cancer and influenced the malignant behaviors of esophageal cancer cells. However, this study dedicates to clarify if lncRNA HCP5 affects the radiosensitivity of esophageal carcinoma. The expression levels of HCP5 in esophageal cancer and adjacent noncancerous tissue were first analyzed on the TCGA database and then detected by qRT-PCR. The related functional experiments were used to investigate whether the radiosensitivity of esophageal squamous cell carcinoma was affected by the inhibition of HCP5. The expression results showed HCP5 is upregulated in esophageal cancers compared to the normal tissues. Meanwhile, knockdown HCP5 further suppressed the proliferation and promoted the apoptosis of esophageal cancer cells treated with a 2 Gy dose of radiotherapy. Moreover, we uncovered that knockdown HCP5 eliminated radiotherapy resistance by modulating the miR-216a-3p/PDK1 axis to inhibit the AKT activation. Finally, rescue experiments pointed that lowering the miR-216a-3p expression weakened the inhibition effect of knockdown HCP5 on cells treated with radiotherapy. To summary, our results indicate that HCP5 is involved in esophageal carcinoma radiotherapy and knockdown HCP5 enhances the radiosensitivity of esophageal carcinoma by modulating AKT signaling activation.

Citing Articles

Exosomal lncRNA HCP5 derived from human bone marrow mesenchymal stem cells improves chronic periodontitis by miR-24-3p/// pathway.

Liu Y, Zhu J, Wang W, Zeng L, Yang Y, Wang Z Heliyon. 2024; 10(14):e34203.

PMID: 39104492 PMC: 11298838. DOI: 10.1016/j.heliyon.2024.e34203.

Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review).

Yan Q, Wong W, Gong L, Yang J, Liang D, Chin K Int J Mol Med. 2024; 54(2).

PMID: 38963019 PMC: 11232667. DOI: 10.3892/ijmm.2024.5396.

The roles and molecular mechanisms of non-coding RNA in cancer metabolic reprogramming.

Li S, Peng M, Tan S, Oyang L, Lin J, Xia L Cancer Cell Int. 2024; 24(1):37.

PMID: 38238756 PMC: 10795359. DOI: 10.1186/s12935-023-03186-0.

Zhang Y, Zhang J, Wang F, Wang L J Oncol. 2023; 2023:6037121.

PMID: 37064863 PMC: 10104744. DOI: 10.1155/2023/6037121.

The roles and mechanisms of the lncRNA-miRNA axis in the progression of esophageal cancer: a narrative review.

Huang T, Wu Z, Zhu S J Thorac Dis. 2022; 14(11):4545-4559.

PMID: 36524088 PMC: 9745524. DOI: 10.21037/jtd-22-1449.

References

Estruch M, Reckzeh K, Vittori C, Centio A, Ali M, Engelhard S . Targeted inhibition of cooperative mutation- and therapy-induced AKT activation in AML effectively enhances response to chemotherapy. Leukemia. 2020; 35(7):2030-2042. DOI: 10.1038/s41375-020-01094-0. View

Zhang H, Si J, Yue J, Ma S . The mechanisms and reversal strategies of tumor radioresistance in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 2021; 147(5):1275-1286. DOI: 10.1007/s00432-020-03493-3. View

Demarest C, Chang A . The Landmark Series: Multimodal Therapy for Esophageal Cancer. Ann Surg Oncol. 2021; 28(6):3375-3382. DOI: 10.1245/s10434-020-09565-5. View

Zhang Y, Chen W, Wang H, Pan T, Zhang Y, Li C . Upregulation of miR-519 enhances radiosensitivity of esophageal squamous cell carcinoma trough targeting PI3K/AKT/mTOR signaling pathway. Cancer Chemother Pharmacol. 2019; 84(6):1209-1218. DOI: 10.1007/s00280-019-03922-2. View

Zou S, Gao Y, Zhang S . lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma. Int J Oncol. 2021; 59(2). PMC: 8253586. DOI: 10.3892/ijo.2021.5236. View

Han S, Wang P, Cai H, Wan J, Li S, Lin Z . Alterations in the RTK/Ras/PI3K/AKT pathway serve as potential biomarkers for immunotherapy outcome of diffuse gliomas. Aging (Albany NY). 2021; 13(11):15444-15458. PMC: 8221357. DOI: 10.18632/aging.203102. View

Wu Y, Zhang J, Zheng Y, Ma C, Liu X, Sun X . miR-216a-3p Inhibits the Proliferation, Migration, and Invasion of Human Gastric Cancer Cells via Targeting RUNX1 and Activating the NF-κB Signaling Pathway. Oncol Res. 2017; 26(1):157-171. PMC: 7844601. DOI: 10.3727/096504017X15031557924150. View

Chen J, Zhao D, Meng Q . Knockdown of HCP5 exerts tumor-suppressive functions by up-regulating tumor suppressor miR-128-3p in anaplastic thyroid cancer. Biomed Pharmacother. 2019; 116:108966. DOI: 10.1016/j.biopha.2019.108966. View

Tang Y, Liu B, Li J, Wu H, Yang J, Zhou X . Genetic variants in PI3K/AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy. Cancer Med. 2015; 5(1):24-32. PMC: 4708901. DOI: 10.1002/cam4.564. View

10.

Peters S . Regulation of PDH activity and isoform expression: diet and exercise. Biochem Soc Trans. 2003; 31(Pt 6):1274-80. DOI: 10.1042/bst0311274. View

11.

Molinaro C, Martoriati A, Lescuyer A, Fliniaux I, Tulasne D, Cailliau K . 3-phosphoinositide-dependent protein kinase 1 (PDK1) mediates crosstalk between Src and Akt pathways in MET receptor signaling. FEBS Lett. 2021; 595(21):2655-2664. DOI: 10.1002/1873-3468.14195. View

12.

Wang C, Li S, Liu J, Cheng M, Wang D, Wang Y . Silencing of S-phase kinase-associated protein 2 enhances radiosensitivity of esophageal cancer cells through inhibition of PI3K/AKT signaling pathway. Genomics. 2020; 112(5):3504-3510. DOI: 10.1016/j.ygeno.2020.04.029. View

13.

Mattiuzzi C, Lippi G . Current Cancer Epidemiology. J Epidemiol Glob Health. 2019; 9(4):217-222. PMC: 7310786. DOI: 10.2991/jegh.k.191008.001. View

14.

Mardanshahi A, Gharibkandi N, Vaseghi S, Abedi S, Molavipordanjani S . The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines. Mol Biol Rep. 2021; 48(8):1-14. DOI: 10.1007/s11033-021-06607-3. View

15.

Zhang W, Hu X, Chakravarty H, Yang Z, Tam K . Identification of Novel Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors by Kinase Activity-Based High-Throughput Screening for Anticancer Therapeutics. ACS Comb Sci. 2018; 20(11):660-671. DOI: 10.1021/acscombsci.8b00104. View

16.

Chang L, Graham P, Ni J, Hao J, Bucci J, Cozzi P . Targeting PI3K/Akt/mTOR signaling pathway in the treatment of prostate cancer radioresistance. Crit Rev Oncol Hematol. 2015; 96(3):507-17. DOI: 10.1016/j.critrevonc.2015.07.005. View

17.

Su M, Xiao Y, Ma J, Cao D, Zhou Y, Wang H . Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications. J Hematol Oncol. 2018; 11(1):118. PMC: 6142629. DOI: 10.1186/s13045-018-0663-8. View

18.

Gao M, Liu L, Yang Y, Li M, Ma Q, Chang Z . LncRNA HCP5 Induces Gastric Cancer Cell Proliferation, Invasion, and EMT Processes Through the miR-186-5p/WNT5A Axis Under Hypoxia. Front Cell Dev Biol. 2021; 9:663654. PMC: 8226141. DOI: 10.3389/fcell.2021.663654. View

19.

Ning M, Qin S, Tian J, Wang Y, Liu Q . LncRNA AFAP-AS1 promotes anaplastic thyroid cancer progression by sponging miR-155-5p through ETS1/ERK pathway. Bioengineered. 2021; 12(1):1543-1554. PMC: 8806209. DOI: 10.1080/21655979.2021.1918537. View

20.

Zhang W, Yu D, Peng J, Xu J, Wei Y . Gastric-tube versus whole-stomach esophagectomy for esophageal cancer: A systematic review and meta-analysis. PLoS One. 2017; 12(3):e0173416. PMC: 5340360. DOI: 10.1371/journal.pone.0173416. View