# The 7SK snRNP complex: a critical regulator in carcinogenesis

Oriana Puidebat, Sylvain Egloff

► To cite this version:

Oriana Puidebat, Sylvain Egloff. The 7SK snRNP complex: a critical regulator in carcinogenesis. Biochimie, 2025, 238, pp.3-8. 10.1016/j.biochi.2025.05.003. hal-05347038

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The 7SK snRNP complex: a critical regulator in carcinogenesis

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Oriana Puidebat¹ and Sylvain Egloff¹, *

¹Molecular, Cellular and Developmental biology unit (MCD), Centre de Biologie
Integrative (CBI), University of Toulouse, CNRS, UPS, 118 route de Narbonne,
Toulouse, Cedex, France.

*Corresponding author: Sylvain Egloff e-mail: sylvain.egloff@univ-tlse3.fr
phone: (33)561335991
fax: (33)561335886
## Summary

Cyclin-Dependent Kinase 9 (CDK9) is a critical regulator of transcriptional elongation, functioning within the Positive Transcription Elongation Factor b (P-TEFb) complex alongside Cyclin T1. P-TEFb facilitates the release of RNA polymerase II (RNAPII) from promoter-proximal pausing, thereby enabling productive transcriptional elongation. CDK9 activity is tightly controlled by the 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, comprising 7SK snRNA, LARP7, MEPCE, and HEXIM1/2. Under homeostatic conditions, the 7SK snRNP sequesters and inactivates a fraction of P-TEFb, maintaining it in a repressed state. However, in response to cellular stress or increased transcriptional demand, P-TEFb is released from 7SK snRNP, activating CDK9 to ensure precise, context-dependent transcriptional control. This regulatory switch allows dynamic adaptation to environmental and intracellular cues. Emerging evidence implicates 7SK snRNP deregulation in cancer progression. This review explores the intricate interplay between 7SK snRNP and CDK9, highlighting how disruptions in individual 7SK snRNP components drive transcriptional imbalances, amplify oncogenic programs, and promote a tumorigenic environment.

## Highlights

* CDK9 drives oncogenic transcriptional programs.

* The 7SK snRNP complex acts as a key negative regulator of CDK9 activity.

* 7SK snRNP dysregulation leads to loss of CDK9 control and transcriptional imbalance.

* Targeting 7SK snRNP components presents a promising therapeutic strategy.

**Keywords:** P-TEFb; CDK9; 7SK snRNP; HEXIM1; cancer; RNA polymerase II; pausing; transcription
# 1 - Introduction

Transcription of protein-coding genes by RNA polymerase II (RNAPII) is a tightly regulated process that ensures messenger RNAs (mRNAs) are produced at the appropriate time and in the correct cell type. To synthesize full-length transcripts, RNAPII must overcome promoter-proximal pausing, a regulatory step where the polymerase is halted 50-100 base pairs downstream of the transcription start site (TSS) by two negative elongation factors: DSIF (DRB Sensitivity-Inducing Factor) and NELF (Negative Elongation Factor) (Fig. 1A). Failure to transition from this paused state to productive elongation results in abortive transcription due to premature termination [1]. The paused RNAPII complex is converted into an elongation-competent state by the positive transcription elongation factor b (P-TEFb), composed of the CDK9 kinase and Cyclin T1/T2 [2]. P-TEFb facilitates this transition by phosphorylating Ser2 residues in the carboxy-terminal domain (CTD) of RNAPII's largest subunit, as well as DSIF and NELF. These phosphorylation events release RNAPII from pausing, enabling productive elongation and full-length mRNA synthesis (Fig. 1A) [1, 2]. RNAPII pausing and release are critical regulatory checkpoints in the transcription cycle, positioning P-TEFb activity as a key determinant of transcriptional output. Active P-TEFb is recruited to target promoters and enhancers through its interaction with BRD4 (Bromodomain-containing protein 4), which recognizes acetylated histones via its bromodomains [3, 4]. Additionally, P-TEFb can integrate into the Super Elongation Complex (SEC), a multiprotein assembly that facilitates RNAPII elongation, particularly during the transcriptional activation of stimulus-responsive genes [5].

In human cells, a significant fraction of P-TEFb is sequestered in a large, catalytically inactive ribonucleoprotein complex (RNP), termed the 7SK/P-TEFb snRNP, which is assembled around the 7SK small nuclear RNA (snRNA) (Fig. 1A) [6]. By maintaining a fraction of P-TEFb in an inactive state, the 7SK/P-TEFb snRNP limits cellular CDK9 availability. Dysregulation of this regulatory system, leading to abnormal P-TEFb activation, can severely impact RNAPII pausing and transcription dynamics. This review focuses on emerging evidence linking the 7SK snRNP to cancer development. Specifically, we explore how disruptions in the P-TEFb regulatory system may promote uncontrolled transcriptional activity, driving accelerated growth in cancer cells.
## 2- P-TEFb activity and oncogenic transcription

1 79 CDK9 is frequently overexpressed or hyperactivated in various cancers, including
2 80 leukemia, lymphoma, breast cancer, prostate cancer and glioblastoma [7]. High CDK9
3 81 expression correlates with poor prognosis across many tumor types. Mechanistically,
4 82 hyperactivation of P-TEFb disrupts the precise regulation of RNAPII pause release, a
5 83 hallmark of cancers addicted to c-MYC or driven by mixed-lineage leukemia (MLL)
6 84 translocations [7, 8]. Elevated CDK9 activity drives oncogenic cancer phenotypes by
7 85 favouring transcription elongation of oncogenes (e.g., MYC), anti-apoptotic factors
8 86 (e.g., MCL-1, BCL-2), and other pro-survival genes, thereby fueling tumor growth (Fig.
9 87 1B) [9]. This dependency on high-level oncogene expression is referred to as
10 88 “transcriptional addiction”, wherein sustained transcriptional activation supports
11 89 uncontrolled cell proliferation [10]. Simultaneously, the activation of anti-apoptotic
12 90 pathways enables cancer cells to evade apoptosis, further promoting tumor survival
13 91 [11]. In MLL-driven leukemia, chromosomal rearrangements involving the MLL (Mixed
14 92 Lineage Leukemia) gene frequently result in fusion with subunits of the SEC complex.
15 93 This aberrant fusion misdirects P-TEFb to MLL target genes, leading to the aberrant
16 94 activation of genes that promote stemness and proliferation while blocking
17 95 hematopoietic differentiation, ultimately resulting in leukemia (Fig. 1C) [12].
18 96
19 97 Beyond these direct effects, increased CDK9 activity can impair DNA repair pathways
20 98 and cellular stress responses, allowing cancer cells to thrive under adverse conditions,
21 99 such as chemotherapy [13, 14]. Moreover, CDK9 has been shown to promote
22 300 epithelial-mesenchymal transition (EMT), a key process in metastasis, by regulating
23 301 transcription of EMT-related genes [15]. This facilitates cancer cell motility and
24 302 invasiveness, contributing to metastatic progression. Accordingly, preclinical studies
25 303 have demonstrated that CDK9 inhibitors can effectively reduce migration and invasion
26 304 in multiple cancer models, including breast cancer, glioblastoma, and pancreatic
27 305 cancer [16].
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treatment of various cancers [17]. CDK9 inhibition may be particularly effective when combined with other anti-cancer therapies. For instance, dual inhibition of BRD4 and CDK9 has been shown to produce synergistic effects by significantly suppressing oncogene transcription [16, 18].

### 3- Regulation of P-TEFb activity by the 7SK snRNP

In human cells, a substantial fraction of P-TEFb exists in an inactive state within the 7SK snRNP. This complex is composed of 7SK snRNA, MePCE (Methylphosphate Capping Enzyme), LARP7 (La-related Protein 7) and HEXIM1/2 (Hexamethylene Bisacetamide-inducible Protein 1/2) (Fig. 1A), with each component playing a specific role in maintaining the stability and regulatory function of the RNP [6]. MePCE and LARP7 binds to the 5' and 3' ends of 7SK snRNA, respectively, ensuring its stability and preserving the structural integrity of the complex [19, 20]. Regulation of P-TEFb activity within the 7SK snRNP relies on HEXIM1/2. A dimer of HEXIM1 and/or HEXIM2 interacts with a hairpin structure in the 5' region of 7SK snRNA, exposing specific binding sites for the CDK9/CyclinT1 complex, which are otherwise masked by the autoinhibited HEXIM1/2 dimer [21]. This interaction allows HEXIM1/2 to bind CDK9, sequestering and inactivating it within the 7SK snRNP. The equilibrium between the active and inactive forms of P-TEFb is highly dynamic and adjusts to the transcriptional needs and proliferative state of the cell [22-24].

Notably, cellular stress -such as transcription blockade, DNA damage or viral infection-triggers the rapid disassembly of the 7SK/P-TEFb snRNP, leading to transient increase in CDK9 activity. Stress-induced dissociation of the 7SK/P-TEFb snRNP involves post-translational modifications of its protein components, post-transcriptional modifications of 7SK snRNA and/or transient structural rearrangement of the RNA. This response is tightly regulated by various signaling pathways activated under stress conditions [2].

One well-documented example of this mechanism occurs in response to UV-induced genotoxic stress, where the dissociation of the 7SK/P-TEFb snRNP provides an additional pool of P-TEFb, enabling the cell to reprogram RNAPII transcription and promote survival. Following UV irradiation, promoter-proximally paused RNAPII is rapidly and synchronously released from pause sites across nearly all active genes, generating a transcriptional wave within gene bodies [25-27]. This wave prioritizes the
expression of short genes, including key UV-response genes, and/or shorter protein isoforms essential for stress adaptation.

In summary, the 7SK snRNP serves as a crucial regulator of P-TEFb activity, dynamically balancing its sequestration and release to adapt transcriptional output to cellular needs. This regulatory mechanism ensures efficient responses to environmental or intracellular stressors, preserving cellular viability and transcriptional integrity.

## 4- Loss of 7SK snRNP integrity in cancers

Given the central role of P-TEFb in regulating RNAPII transcription, it is not surprising that malfunction of the 7SK/P-TEFb regulatory machine contributes to human diseases. The first clear link between 7SK/P-TEFb snRNP disruption and human pathologies was established in cardiac hypertrophy, where hypertrophic signals lead to uncontrolled disassembly of the 7SK/P-TEFb complex, shifting the P-TEFb equilibrium towards its active form [28]. This results in enhanced RNAPII transcription, increased mRNA and protein synthesis, and cardiomyocytes enlargement [29]. More recently, growing evidences has implicated deregulation of 7SK snRNP in cancer, often leading to profound transcriptional reprogramming. All major components of the 7SK snRNP have been associated with cancer development or progression, underscoring its critical role in maintaining transcriptional homeostasis.

### 4.1- Expression and modification of 7SK snRNA

As the structural scaffold of the inhibitory 7SK/P-TEFb snRNP, 7SK snRNA is pivotal in regulating P-TEFb activity. Reduced accumulation of 7SK snRNA is frequently observed in cancers and correlates with increased P-TEFb activity [30]. For example, low levels of 7SK snRNA have been reported in tissue samples from breast, blood, and colon cancers. Overexpression of 7SK snRNA in HEK293T cells suppresses cell viability and enhances apoptosis, highlighting 7SK's ability to restrain proliferation and promote programmed cell death [31].

In tongue squamous cell carcinoma (TSCC), 7SK expression inversely correlates with tumor size. Knockdown of 7SK snRNA in TSCC cells (e.g., SCC15 cells) promotes cell proliferation, migration, and xenograft tumor formation in nude mice [32]. These findings position 7SK snRNA as a potential tumor suppressor in TSCC. Similarly, in triple-negative breast cancer (TNBC) cells, exosomal delivery of 7SK snRNA reduces
tumorigenic phenotypes [33]. This is likely mediated through transcriptional repression of HMGA1 expression, a chromatin-associated protein involved in metastatic progression, as well as other genes involved in apoptosis and epithelial-mesenchymal transition (EMT). These results underscore the therapeutic potential of 7SK snRNA delivery via exosomes as a novel anticancer strategy.

In addition to its intracellular abundance, post-transcriptional modifications of 7SK snRNA also influence P-TEFb activity in cancer cells. In non-small cell lung cancer (NSCLC) cells, activation of the m6A methyltransferase METTL3 via epidermal growth factor (EGF) signalling leads to m6A methylation of 7SK snRNA at multiple sites [34]. These modifications induce structural rearrangements in 7SK snRNA, promoting the disassembly of the 7SK/P-TEFb complex (Fig. 2A). Consistently, m6A modification of 7SK snRNA is more abundant in NSCLC cells than in non-malignant cells, and inhibition of this modification of 7SK markedly reduces colony formation. Thus, METTL3-driven 7SK methylation represents a mechanism by which cancer cells hijack P-TEFb activity to sustain aberrant transcriptional programs.

## 4.2- Role of MePCE and LARP7 in cancer

MePCE is a critical component of the 7SK snRNP complex. By capping the 5' end of 7SK snRNA, MePCE protects it from exonucleolytic degradation, ensuring the stability of the 7SK snRNP complex [20, 35]. Dysregulation of MePCE could theoretically destabilize the 7SK snRNP. However, evidence for altered MePCE expression in cancers remains limited. This may be due to MePCE's dual role: it also caps U6 spliceosomal snRNA [36], essential for RNA splicing. Significant reductions or mutations in MePCE could disrupt both transcriptional and splicing processes, likely resulting in lethal cellular effects rather than promoting tumor growth. These dual essential functions may explain the rarity of MePCE mutations in cancers.

LARP7, on the other hand, specifically binds to the 3' end of 7SK snRNA, stabilizing it and maintaining the integrity of the 7SK snRNP complex [19, 37]. The C-terminal domain of LARP7, which is required for binding to 7SK snRNA, is frequently deleted in human tumors due to microsatellite-associated mutations. Mutations, reduction or loss of LARP7 destabilizes 7SK snRNA, impairing 7SK snRNP assembly and leading to P-TEFb-dependent transcriptional reprogramming, which promotes tumorigenic processes (Fig. 2A) [19]. LARP7 has been identified as a tumor suppressor in both
gastric and breast cancers [15, 38], and its expression is reduced in cervical cancers [39]. In gastric cancer (GC), LARP7 expression is significantly down-regulated, correlating with increased cell proliferation and migration [38]. In breast cancer, reduced LARP7 levels redistribute P-TEFb to the super elongation complex, driving EMT, as evidenced by upregulation of EMT markers (e.g., N-cadherin, vimentin) and downregulation of epithelial markers (e.g., E-cadherin). EMT is triggered by increased expression of transcription factors like Slug, FOXC2, ZEB2, and Twist1, and enhances invasion, metastasis and chemotherapy resistance [15]. Breast cancer patients with low LARP7 levels show shorter relapse-free survival after chemotherapy than patients with high LARP7 [40], highlighting its role in therapy resistance. In papillary thyroid carcinoma (PTC), LARP7 suppresses Sonic Hedgehog (SHH) signalling, inhibiting cell proliferation, enhancing apoptosis, and increasing iodine uptake - key for PTC treatment [41]. This intriguing link to SHH signalling suggests therapeutic potential in targeting SHH-related pathways in certain cancers.

Interestingly, both MePCE and LARP7 are synthetic lethal interactors of BRCA1 [42]. In BRCA1-mutated cancer cells, depletion of MEPCE or LARP7 disrupts P-TEFb regulation, leading to transcription-replication collisions, accumulation of R-loops, and DNA double-strand breaks. This highlights the vulnerability of BRCA1-deficient cells to transcriptional dysregulation, presenting a promising therapeutic avenue through targeting RNAPII pausing and the 7SK snRNP complex.

### 4.3- HEXIM1 in cancer pathways

HEXIM1 plays critical roles in various cancer-related pathways. Although it is well established that HEXIM1 functions as part of the 7SK snRNP complex [21], some of its functions occur independently, highlighting its versatility and broader impact in cancer (Fig. 2A). While HEXIM2 shares functional similarities with HEXIM1 [43], its specific role in cancer remains less explored.

HEXIM1 interacts directly with p53 and its regulators, NPM and HDM2 [44, 45]. By blocking HDM2-mediated p53 ubiquitination, HEXIM1 enhances p53 stability and promotes the expression of p53 target genes like *p21* and *PUMA* to regulate cell cycle arrest and apoptosis (Fig. 2A) [45]. This interaction occurs with the 7SK snRNA-free form of HEXIM1, indicating that HEXIM1 regulates p53 independently of P-TEFb. HEXIM1 is a key regulator of p53 induction and activation in response to UV radiation
or treatment with CDK inhibitors, which release HEXIM1 from the 7SK snRNP complex [45]. This disassembly of the 7SK/P-TEFb snRNP complex may provide additional HEXIM1 to activate p53. Accordingly, increased p53 levels under these conditions correlate with enhanced interaction between p53 and HEXIM1. Knockdown of HEXIM1 blocks p53 induction and prevents p53-mediated cell cycle arrest. Given p53's role in angiogenesis and metastasis, HEXIM1 may inhibit tumor progression through activation of p53. Additionally, HEXIM1 is a substrate of HDM2, a negative regulator of p53 [46]. HDM2 ubiquitinates HEXIM1, but unlike p53, this modification does not lead to its proteasomal degradation. Instead, ubiquitinated HEXIM1 exerts a stronger inhibitory effect on P-TEFb. Since HEXIM1 and p53 share similar ubiquitination sites, it has been proposed that HEXIM1 competes with p53 for binding to HDM2, potentially stabilizing p53 and enhancing its function. Concurrently, the increased inhibition of P-TEFb would suppress RNAPII transcription. Loss of HEXIM1 function could, therefore, lead to decreased p53 stability and increased RNAPII transcription—two factors that contribute to oncogenesis.

HEXIM1 is a key tumor suppressor in breast cancer, particularly in triple-negative breast cancer (TNBC), where downregulation of HEXIM1 is associated with increased cell proliferation and migration [47]. In estrogen receptor (ER)-positive breast cancer, HEXIM1 inhibits ERα-mediated transcription by competing with Cyclin T1 for ERα binding, limiting estrogen-driven tumor growth [48, 49]. HEXIM1 also interacts with the p65 subunit of NF-κB, a transcription factor implicated in inflammation and cancer progression (Fig. 2A). Like for ERα, HEXIM1 inhibits NF-κB's transcriptional activity by competing with P-TEFb for p65 interaction, thereby suppressing tumor-promoting processes [50].

HEXIM1 plays a role in tumor progression by regulating angiogenesis, a key process for transitioning tumors from benign to malignant states [51]. Under normal conditions, it inhibits estrogen-induced VEGF transcription by preventing ERα recruitment to the VEGF promoter, possibly in a P-TEFb-independent manner [52]. Under hypoxic conditions, HEXIM1 suppresses the expression and recruitment of HIF-1α, a key transcription factor that plays a crucial role in the cellular response to low oxygen conditions, to the VEGF promoter. HEXIM1 directly interacts with HIF-1α, promoting its ubiquitination and subsequent downregulation, thereby reducing angiogenesis.
Finally, HEXIM1 is also emerging as a promising therapeutic target in acute myeloid leukemia (AML). In AML, HEXIM1 induction enhances the anti-AML effects of JQ1, a BET protein antagonist, by promoting apoptosis and suppressing oncogenes like c-Myc, thus halting leukemia progression [53]. An interaction between HEXIM1 and nucleophosmin (NPM), a key regulator of p53 that stabilizes and enhances its activity, has been identified. Mutations in NPM, which cause its mislocalization to the cytoplasm (NPMc+), are commonly observed in acute myeloid leukemia (AML). The NPMc+ variant has been shown to sequester HEXIM1 in the cytoplasm, thereby reducing its nuclear levels [54]. Such cytoplasmic mislocalization of HEXIM1 would disrupt the balance between active and inactive P-TEFb complexes in the nucleus, favoring an increase in active P-TEFb. Accordingly, elevated P-TEFb-mediated transcription has been observed in NPMc+ AML cell lines, highlighting a link between HEXIM1/P-TEFb dysregulation and AML tumorigenesis.

## 5- Concluding remarks

The 7SK snRNP complex, a critical regulator of RNAPII transcription homeostasis, has emerged as a significant player in carcinogenesis. Dysregulation of the 7SK snRNP leads to abnormal P-TEFb activation, driving oncogenic transcription and promoting tumor progression (Fig. 2B). As mentioned in this review, studies have shown that inhibiting CDK9 or modulating the expression of 7SK snRNP components have therapeutic potential. For instance, re-establishing 7SK snRNA stability and rebalancing P-TEFb activity could suppress oncogenic transcription program and enhance the effectiveness of other treatments. This reinforces the idea of developing anti-cancer treatments through combinational therapy.

## Acknowledgements

OP and SE are supported by grants from la Ligue Nationale contre le Cancer, and the Agence Nationale de la Recherche (ANR-23-CE12-0009-01 to S.E.).

## Conflict of interests

The authors declare no conflict of interests.

## Figure Legends
<caption>**Figure 1: P-TEFb in Cancer: Function, Regulation and Aberrant Targeting.**</caption>

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(A) P-TEFb (CycT1/CDK9) activity is tightly regulated by the 7SK snRNP complex, which consists of 7SK snRNA, MePCE, LARP7, and HEXIM1. In cells, a dynamic equilibrium exists between the active, free form of P-TEFb and its inactive form sequestered in the 7SK snRNP. Upon recruitment to gene promoters, active P-TEFb phosphorylates Ser2 in the CTD of RNA polymerase II (RNAPII) and the negative elongation factors NELF and DSIF (red circles). These phosphorylation events release NELF and convert DSIF into a positive elongation factor, facilitating RNAPII escape from the promoter and enabling productive transcription elongation. TSS: transcription start site.

(B) In pathological conditions, P-TEFb mistargeting by BRD4 or MYC leads to oncogene hyperactivation (e.g., *c-MYC*, *BCL-2*, *VEGF*), promoting cell proliferation, migration, invasion, and angiogenesis—hallmarks of breast cancer, lung cancer, and acute myeloid leukemia (AML).

(C) In leukemia, aberrant P-TEFb recruitment by the chimeric Super Elongation Complex/Mixed Lineage Leukemia (SEC/MLL) complex drives the overactivation of leukemia-inducing *HOX* genes, contributing to disease progression.

<caption>**Figure 2: Misregulation of 7SK components promotes oncogenic processes.**</caption>

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(A) Downregulation or mutation of 7SK chaperones (MePCE and Larp7), Hexim1, or post-transcriptional modifications of 7SK snRNA shift the balance of P-TEFb toward its active form, leading to its over-activation (blue line). Beyond its role in the 7SK snRNP, Hexim1 stabilizes p53 and inhibits key transcription factors, including HIF-1α, NF-κB, and estrogen receptor α (ERα). Reduced Hexim1 levels not only drive 7SK/P-TEFb snRNP disassembly but also destabilize p53 and activate tumor-promoting transcription factors (red lines), collectively enhancing cell survival and oncogenic transcription.

(B) Cancer types linked to the dysregulation of 7SK snRNP components (with associated references in parentheses).

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A

<figure><img src="image_3.png" /><figcaption>**Figure 1: P-TEFb in Cancer: function, regulation and aberrant targeting**</figcaption></figure>

B

<figure><img src="image_4.png" /></figure>

C

<figure><img src="image_5.png" /></figure>

(A) P-TEFb (CycT1/CDK9) activity is tightly regulated by the 7SK snRNP complex, which consists of 7SK snRNA, MePCE, LARP7, and HEXIM1. In cells, a dynamic equilibrium exists between the active, free form of P-TEFb and its inactive form sequestered in the 7SK snRNP. Upon recruitment to gene promoters, active P-TEFb phosphorylates Ser2 in the CTD of RNA polymerase II (RNAPII) and the negative elongation factors NELF and DSIF (red circles). These phosphorylation events release NELF and convert DSIF into a positive elongation factor, facilitating RNAPII escape from the promoter and enabling productive transcription elongation. TSS: transcription start site.

(B) In pathological conditions, P-TEFb mistargeting by BRD4 or MYC leads to oncogene hyperactivation (e.g., c-MYC, BCL-2, VEGF), promoting cell proliferation, migration, invasion, and angiogenesis—hallmarks of breast cancer, lung cancer, and acute myeloid leukemia (AML).

(C) In leukemia, aberrant P-TEFb recruitment by the chimeric Super Elongation Complex/Mixed Lineage Leukemia (SEC/MLL) complex drives the overactivation of leukemia-inducing HOX genes, contributing to disease progression.
A

<figure><img src="image_6.png" /><figcaption>Figure 2: Misregulation of 7SK components promotes oncogenic processes.</figcaption></figure>

B

<figure><img src="image_7.png" /></figure>

(A) Downregulation or mutation of 7SK chaperones (MePCE and Larp7), Hexim1, or post-transcriptional modifications of 7SK snRNA shift the balance of P-TEFb toward its active form, leading to its over-activation (blue line). Beyond its role in the 7SK snRNP, Hexim1 stabilizes p53 and inhibits key transcription factors, including HIF-1α, NF-κB, and estrogen receptor α (ERα). Reduced Hexim1 levels not only drive 7SK/P-TEFb RNP disassembly but also destabilize p53 and activate tumor-promoting transcription factors (red lines), collectively enhancing cell survival and oncogenic transcription.

(B) Cancer types linked to the dysregulation of 7SK snRNP components (with associated references in parentheses).