piR‐823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1

Abstract

Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.

piR‐39980 promotes cell proliferation, migration and invasion, and inhibits apoptosis via repression of SERPINB1 in human osteosarcoma

“…Cheng et al (2012) revealed that piR-823 was significantly downregulated in gastric cancer tissues and acted as a tumour suppressor in human gastric cancer cells [Cheng et al, 2012]. In contrast, Yin et al (2017) reported that piR-823 was significantly upregulated in colorectal cancer tissues and promoting colorectal tumourigenesis by augmenting transcriptional activity of Heat shock factor 1 (HSF1; Yin et al, 2017). There are few more studies like this reporting piR-NAs playing differently in different cancers [Cordeiro et al, 2016], sometimes as a tumour suppressor in one and as an oncogene in other, which portray the multifaceted regulatory functions of piRNAs in human cancers.…”

“…These are of ß26-36 nucleotides (nts) in length characterised by a 3-terminal 2´-Omethylation and are now reported in somatic and cancer cells regulating differentiation, development, proliferation, apoptosis, invasiveness, angiogenesis, chemo-resistance and so on besides their germline functions [Bahn et al, 2015;Khurana and Theurkauf, 2010;Xiong et al, 2015;Weng et al, 2018;Firmino et al, 2016]. More specifically, only a few piRNAs such as piR-651, piR-20365, piR-021285, piR-932 and piR-823 have been reported to regulate oncogenesis of various cancers such as breast, pancreas, lung, kidney, colorectal, cervical, head, neck and gastric cancer [Zhang et al, 2013;Li et al, 2016;Cordeiro et al, 2016;Fu et al, 2015;Yin et al, 2017]. These studies revealed that piRNAs are promising small ncRNAs in cancer research for their prognostic, diagnostic and therapeutic potential.…”

Small non‐coding RNA and colorectal cancer

“…III. 100 109 The production of tRF-5s Then, pri-miR-NAs are processed to generate miRNA precursors (pre-miRNAs) by RNase III Drosha in complex with DGCR8, a RNA-binding protein functioning as a ruler to measure cleavage point.…”

Tumor suppressive activity of PIWI‐interacting RNA in human fibrosarcoma mediated through repression of RRM2

“…Cheng et al reported that the expression of piR‐823 in gastric cancer tissues was significantly lower compared to non‐cancerous tissues and its increased expression inhibited growth of gastric cancer cells . In contrast, Yin et al showed that same piRNA was significantly upregulated in colorectal cancer and acting as oncogene contributing to its tumorigenesity . Similarly, piR‐651 is upregulated in lung cancer and regulate carcinogenesis by influencing cell proliferation, apoptosis, migration and invasion .…”

“…Further, aberrant expression of piRNAs has been documented in cancers such as breast, pancreas, lung, kidney, colorectal, cervical, head, neck, and gastric cancer . However, only a few piRNAs such as piR‐651, piR‐20365, piR‐021285, piR‐932, and piR‐823 have been intensively explored and validated in different cancers to decipher their role in oncogenesis . Cheng et al reported that the expression of piR‐823 in gastric cancer tissues was significantly lower compared to non‐cancerous tissues and its increased expression inhibited growth of gastric cancer cells .…”