Open Access

ARTICLE

Silencing of the long non-coding RNA LINC00265 triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene

by XIAOBI HUANG^1,#, CHUNYUAN CHEN², YONGYANG CHEN^1,#, HONGLIAN ZHOU¹, YONGHUA CHEN¹, ZHONG HUANG¹, YULIU XIE¹, BAIYANG LIU¹, YUDONG GUO¹, ZHIXIONG YANG¹, GUANGHUA CHEN^3,*, WENMEI SU^1,4,*

1 Department of Pulmonary Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China
2 Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China
3 Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China
4 Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China

* Corresponding Authors: GUANGHUA CHEN. Email: ; WENMEI SU. Email:

Oncology Research 2024, 32(7), 1185-1195. https://doi.org/10.32604/or.2023.030771

Received 21 April 2023; Accepted 22 August 2023; Issue published 20 June 2024

Abstract

Background: Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood. Methods: Here, the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts. Results: We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients, whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis. Moreover, we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma. Conclusions: Our findings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.

---

Keywords

---

Supplementary Material

Supplementary Material File

---