The lncRNAs LINC00261 and LINC00665 are upregulated in long-term prostate cancer adaptation after radiotherapy

Abstract

Long non-coding RNAs (lncRNAs) have been shown to impact important biological functions such as proliferation, survival, and genomic stability. To analyze radiation-induced lncRNA expression in human tumors, we irradiated prostate cancer cells with a single dose of 10 Gy or a multifractionated radiotherapeutic regimen of 10 fractions with a dose of 1 Gy (10 × 1 Gy) during 5 days. We found a stable upregulation of the lncRNA LINC00261 and LINC00665 at 2 months after radiotherapy that was more pronounced after single-dose irradiation. Analysis of the The Cancer Genome Atlas (TCGA) and The Atlas of Non-coding RNAs in Cancer (TANRIC) databases showed that high expression of these two lncRNAs may be a potential negative prognostic marker for overall survival of prostate cancer patients. Knockdown of LINC00261 and LINC00665 in long-term survivors decreased survival after re-irradiation and affected DNA double-strand break repair. Mechanistically, both lncRNAs showed an interdependent expression and regulated expression of the DNA repair proteins CtIP ( RBBP8 ) and XPC as well as the microRNA miR-329 . Identifying long-term tumor adaptation mechanisms can lead to the discovery of new molecular targets, in effect opening up new research directions and improving multimodal radiation oncologic treatment.

Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner

“…Irradiation was performed at room temperature using single doses or multiple fractions of 320 kV X-rays with a dose-rate of 2.3 Gy/min (Precision X-Ray Inc.). Multifractionated radiation was carried out as described before with two times 1 Gy per day (with a 6 h time interval between both radiations) 34 . At 24 h after the final radiation dose or 6 d after the first radiation dose (Supplementary Figure S1), total RNA was extracted for short-term (ST) gene analysis (Fig.…”

“…Total RNA was extracted from three replicates using a QIA shredder spin column (Catalog no. 79654, Qiagen) as published previously 34 . The RNeasy mini kit (Qiagen) was used to purify the extracted RNA.…”

The Emerging Roles of LINC00665 in Human Cancers

“…These results revealed that LINC00665 could inhibit the expression of KLF2 by interacting with EZH2 and LSD1 to promote prostate cancer progression ( Xue et al, 2021 ). In particular, one study showed that LINC0065 was steadily upregulated in prostate cancer cells 2 months after radiotherapy ( Eke et al, 2021 ). This study proved that LINC00665 regulated RBBP8, XPC, and BRCA1 gene expression ( Eke et al, 2021 ).…”

LINC00261 Inhibits Esophageal Cancer Radioresistance by Down-Regulating microRNA-552-3p and Promoting DIRAS1

“… 6 One such LINC, namely LINC00261, is known to be insufficiently expressed in a wide variety of cancers, ranging from pancreatic cancer, colon cancer, to prostate cancer, while newer studies have also implicated LINC00261 with cancer cell viability, mobility radioresistance, and poor prognosis. 7–9 Regarding EC, LINC00261 can promotes EC cell sensitivity to drugs, whereas, silencing of LINC00261 was previously shown to augment EC growth and diminish apoptosis and sensitivity. 10 Mechanistic-based studies have also indicated that LINC00261 can mediate tumorigenesis and cancer progression by means of competing endogenous RNA (ceRNA) interactions.…”